Journal of Cell Science eateto ilg,Uiest fNrhCrln tCae il hplHl,N 71,USA 27514, NC Hill, Chapel Hill, Chapel at Carolina North of University Biology, Salmon of D. Department E. and the Varma* Dileep of conductors chief orchestra – kinetochore network protein KMN The Commentary sCS5o lni nhmn,Sc0 nyatadSc0Rin known Spc105R and (also yeast in KNL1 Spc105 humans, of in blinkin consists or CASC5 vertebrates as in which and complex, Maresca 2009; and Musacchio, (Cheeseman and network 2010). Salmon, Santaguida KMN the 2008; in with errorDesai, role attachment concert central and in attachments a kMT correction has of 1B), stability (Fig. the The regulating concentrations 2012). high before chromatin Fukagawa, at centromeric and to anaphase localizes and Takeuchi which B, Hori 1992; Aurora 2008; al., kinase al., al., et et Nishino Saitoh et KMN 2011; 2012; (Hori Fukagawa, MT-binding and 1B) Perpelescu DNA (Fig. the 2012; centromeric domain Fukagawa, link to inner domain to the ‘outer’ is within kinetochore CCAN the -X, in and of -W network function -U, -T, major -S, (CCAN). 1B) -P, A network’ -O, (Fig. centromere-associated -N, ‘constitutive -M, kinetochore the -L, called -K, consisting the -I, proteins -H, centromeric CENP-C, of peripheral of of domain CENP-A-containing complex a to ‘inner’ contains each addition of the In periphery 1B). chromatin, the (Fig. at centromere nucleosomes (Cse4 sister within humans in yeast), CENP-A budding H3, histone in modified a of by determined presence is the assembled are Musacchio, kinetochores microtubules and where site spindle Santaguida The 2008; 2009). of Desai, ends and plus (Cheeseman the (MTs) to that DNA kinetochores within centromeric architecture Knl1links protein below) the see the of complex; part for Ndc80 is the network (named and complex KMN Mis12 The the complex, 1B). to localize (Fig. that kinetochores complexes, major human more or ten 80 over in identified proteins, has different 1A). decades two (Fig. past mitosis the of over at research onset Extensive the formed at chromosomes are of centromeres that the assemblies mega-molecular are Kinetochores Introduction highly a the kinetochores, the for at network between KMN reside interface the proteins primary of cells. the words: role motor human the Key as MT of on years understanding that focus recent our years a in in with advances emerged 30 recent functions, has a over summarize kinetochore network, acquiring will for key KMN kinetochore Commentary known the This sister checkpoint kMTs. been called each assembly and complexes, spindle with has kinetochore the protein alignment it of of metaphase control Although generation network achieve and force kMTs. conserved chromosomes attachment; anchorage; kMT of until kMT microtubules sister in dynamic anaphase complement other spindle errors and delays the of robust full of typically and correction functions: ends pole dynamics; key SAC plus-end four spindle plus The least kMT one (SAC). the at to to provide coupled to sister attachment be one end-on kMT can tether for that attached that Sites (kMTs) become pole. microtubules opposite kinetochores the kinetochore to sister forming thereby that prometaphase, requires in (MTs) mitosis of completion Successful Summary ( correspondence for *Author o:10.1242/jcs.093724 doi: 5927–5936 125, ß Science Cell of Journal 02 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2012. h ihycnevdKNntokicue h Knl1 the includes network KMN conserved highly The hcpit ieohr,KL,MS2 ioi,NDC80 Mitosis, MIS12, KNL1, Kinetochore, Checkpoint, [email protected] ) n hh 02.TeKNntoki lotogtt associate to thought also assembly is spindle network KMN the The Kops 2012). 2007; of Salmon, Shah, and and members (Musacchio These 1B) and (Fig. kinetochore (SAC) localization. checkpoint plus-ends of kinetochore proximity (kMT) the their MT in proteins for MT-associated of network include members of KMN presence the the on depend domain 2009). outer kinetochore al., et al., Wan et 2007; Schittenhelm al., are 2011; 2006; et al., al., and Schittenhelm et et Przewloka 2009; complex, (DeLuca 2009; metaphase Mis12 al., at et the axis Joglekar from kMT or outwards the CENP-T along extending oriented with shape, complex chromatin elongated junctions Ndc80 Mis12 an the their CENP-A-containing have the Both 2012). KNL1 to Fukagawa, to and end, and (Hori is inner CENP-C complex 1B) its Mis12 (Fig. The at through 2010). and, al., et linked kMTs (Petrovic to 1B) binds, (Fig. end, also complex KNL1 outer 2010). al., its et 2012) (Petrovic at Fukagawa, complex and Mis12 (Hori the CENP-T to 2009; or protein anchored CCAN is Musacchio, end the inner and to the either Santaguida whereas 2011), 2010; Stukenberg, and spindle al., Tooley of et Cheeseman, ends telophase and Joglekar plus Gascoigne the 2011; 2012; in Musacchio, for Ndc80 and site the (DeLuca binding in kinetochores of MTs primary end the kinetochores outer from is The complex with 2009). Musacchio, disappears associates and al., (Santaguida et network and Kops 2006; KMN al., prophase et The al., DeLuca et 2004; (Cheeseman 2005). al., SPC25 et (also and Cheeseman NDC80 SPC24 2006; NUF2, comprising HEC1), complex as Ndc80 known four-subunit (also in the called DSN1 KNL-3 four and and (also humans; PMF1) in the NSL1 as MIS13 known as yeast), of (also known in NNF1 consisting MIS14), MIND complex or or DC31 Mis12 (Mtw1 the MIS12 proteins ZWINT; and fly) ubro te rtiswti n tteprpeyo the of periphery the at and within proteins other of number A anradtselegans Caenorhabditis 5927 ); Journal of Cell Science enfudta h -emnlti fteNL uui sal to able is has subunit NSL1 it the network, of tail KMN C-terminal human the that the found entire of been be the components of of to purified basis length found using the the been On of have complex. much subunits yeast 2010). spanning Nsl1 al., them and et with Maskell Dsn1 elongated, 2011; yeast al., the et ‘comma’ Both (Hornung a have shape to bi-lobbed proposed been or has complex yeast the although irsoyaayi ftehmlgu es t1complex Electron Mtw1 2010). yeast al., homologous et the Petrovic assembled 2010; of al., analysis et microscopy kinetochores vertebrate (Maskell DSN1 within 2) MIS12, outside, NNF1, (Fig. to order inside subunits the from the in NSL1, with other and shaped, each rod outer to and tethered for kinetochore long linearly platform 22-nm human the is The major complex 2008). as a Mis12 Desai, as and to (Cheeseman serves referred assembly it kinetochore been as complex, has ‘keystone’ complex Mis12 in The two involved complex other Mis12 mechanisms The network. the and KMN the a of proteins of with function close function the other and controlling complexes, and on Ndc80 and structure discussion Knl1 the the ensure continue components, then to describe complex, Mis12 kinetochore the to network, the KMN inner-most the the of of with member begin functions We segregation. key roles chromosome the potential accurate the of their function and achieving and network in KMN structure with the associated of recent proteins only discuss knowledge KMN will our are we in between Commentary, proteins advances this kinetochore interactions In unraveled. domain the Desai, being outer just of other and nature and (Cheeseman network outer precise 1B) The the cytoplasmic (Fig. 2008). the of and complex CENP-E region kinesin dynein–dynactin the peripheral as MT such and proteins, CENP-F, the as motor such form proteins, fibrous exten including that also kinetochore, prom probably at details. proteins proteins attachments for these text kMT region, See of network. peripheral with absence KMN the the the within to in primarily connected particularly are Although these domain. proteins, of outer associated many the because their kinetoch in domain as outer outer found well the the also as within of are parts dynein, network SAC fib and KMN the long contains CENP-E the of domain outer components motors to the Protein of microtubule chromatin region peripheral the CENP-A-containing The proteins. associated CENP-F, links their and as domain kMTs between such kinetochore interface major inner the is the network KMN within The ( domain. network microtubules. protein spindle CCAN to cells. The mitotic attach CENP-A. in and kinetochore vertebrate chromosomes the mitotic of on structure domain centromeres and composition Protein 1. Fig. 5928 ora fCl cec 2 (24) 125 Science Cell of Journal nvitro in setal ilsasmlreogtdstructure, elongated similar a yields essentially A Mitotic cell kMTs nvitro in Kinetochore assembled at thecentromere rti sebyassays assembly protein Chromosome B [contains dynein,CENP-F, CENP-E h ieo ieohr sebyi pcfe ytepeec ftemdfe itn H3 histone modified the of presence the by specified is assembly kinetochore of site The ) Outer kinetochore(unattached) and theSACproteins] B efrsipratfntosi otoln pnl structure, spindle controlling complex in Mis12 Mis12 the functions the of that important demonstrated studies performs have Seminal chromosome yeast 2006). in and al., homologue stable et bi-orientation alignment, (Kline kinetochore chromosome segregation metaphase formation, subunits in various kMT defects its depleting in complexes, Knl1 results and Ndc80 recent the and of 2012). 2006), al., et al., (Chan microtubule-associated Ska the et complex with (MAP) interacts (Cheeseman protein it that KNL1 indicates it of evidence Ndc80 though the even and of MTs, affinities MT-binding purified complex the to enhance DNA. to bind reported to centromeric been shown site, has attachment been inner MT not core the the has of Mis12 component to that key a machinery as kinetochore the isolated al., of Initially outer part et integral the Okada an with is connects 2006; complex associates al., functional Mis12 directly the et turn 2006), yeast in (Foltz CCAN chromatin the As COMA CENP-A-containing 2011). called with al., complex et directly Ctf19-containing (Hornung a associate CCAN, of and to homologue complex also has shown Mis12 complex is Mtw1 yeast the been subunit The 2011). between Nnf1 al., et interaction centromere-proximal (Przewloka in CENP-C the the interactions that in shown these instrumental been in has In involved it 2011). al., et are (Screpanti cells subunits vertebrate the complex of which their clear Mis12 not is in it CENP-C, with directly variations interacts complex functions. show similar very might perform complexes essentially they Mis12 structure, human to 2011). the though yeast al., link even et that direct and (Hornung suggests yeast a complex evidence the current Ndc80 KNL1 has the of the Hence, complex of of analysis Spc25 the C-terminus similar and that A the Spc24 suggests 2010). to complex al., and Mtw1 inner et complex, the (Petrovic at Ndc80 2) located (Fig. are the which of SPC25, and end SPC24 both to attach ossetwt oeo h i1 ope nterecruitment the in complex Mis12 the of role a with Consistent Mis12 the of end inner the that shown been has it Although CENP-A Aurora B ( A ieohrsaeasmlda h eihr fsister of periphery the at assembled are Kinetochores ) Sister chromatids kinetochore) (inner CCAN kinetochore) (outer KMN network kMTs rspiamelanogaster Drosophila noteinner the into d osproteins, rous etaphase. ore , Journal of Cell Science olrdta nsi h TbnigC rha oan ortt rtita nlsbten0ad120 and 0 between angles the at allowing twist flexible, or highly rotate is to complex (Guimaraes domains kinetochores Ndc80 unattached head the at or of MAD2 region CH and MT-binding loop kinetoc MAD1 internal the inner proteins conserved in the checkpoint The ends to of 2008). complex that retention al., Ndc80 rod the et the coil for Miller bipartite link important 2002; a to be al., complex form heterotetramerize to major et Mis12 subunit Martin-Lluesma shown which the the 2008; NDC80 been SPC25, or al., also is the CENP-T and has right) of to NDC80 SPC24 regions (bottom bind of NUF2, SPC25 tail complex domain and (HEC1), unstructured CH Ndc80 SPC24 charged NDC80 The human of and subunits domains The domain C-terminal four complex. globular CH of the N-terminal Ndc80 consist whereas The the interface, indicated. and and kinetochores (P as complex KNL1 regions at Mis12 with coiled-coil module complex the their attachment tight through with a MT interacts forms core and ZWINT the KNL1 that of of shown domain component coiled-coil been C-terminal also the has binds that It protein 2010). kinetochore rich coiled-coil small relatively ZWINT), a partner is its and MIS12 to binds it (where ope eotdi es)sgetn htteM-on ofraino h d8 ope nhmnclsi lgtybn uigmtpae(a tal. et (Wan metaphase during bent slightly th Ndc80 is of the cells domain of human head confirmation in the extended complex and 57-nm-long Ndc80 domain the the CH to of NDC80 confirmation compared MT-proximal MT-bound (as the the kinetochores between that human suggesting distance in yeast) the nm in that 45 reported observed complex about been only also is has complex It SPC24–SPC25 2009). centromere-proximal al., et (Wan kinetochores metaphase is NDC80 of domain l,20) ua N1(o ih)i ag ut-oanpoenwt h nw ucinldmisadmtf niae.KL seogtdwt t N its with elongated is KNL1 indicated. motifs and domains functional known located the site, with MT-binding protein proposed multi-domain the large contains a which is region, right) (top KNL1 Human 2009). al., and complex Ndc80 rpsdta hssbnthsbe ucinlyrpae npr by part in replaced functionally been has subunit this that in proposed homologue Dsn1 have a investigations identify extensive to segregation Interestingly, failed chromosome 2011). al., in et defects (Venkei Yanagida, similar exhibit and also Goshima subunits 1999; al., et 2000). (Goshima separation biorientationand centromere sister segregation, chromosome accurate located is complex Mis12 the that shown has DNA-proxima a outer imaging centromeric that the fluorescent at whereas NSL1 two-color network KNL1, High-resolution and and KMN o complex DSN1 network. the tail Ndc80 MIS12, CCAN C-terminal the between The NNF1, with the connection interacting 2010). subunits for to al., key four important et binds is the of (Petrovic complex indicated forms consists the sequence yellow) left) of the end top in in outer kinetochores kinetochore-proximal the (shown the of on CCAN axis inside–outside (shown The the complex blue). along Mis12 linearly light arranged human apparently in The (shown chromatin. centromeric kMTs the of and axis kinetochores the network. along KMN projected the is of and composition and Structure 2. Fig. Drosophila , Centromeric 1 , 5n usd fCN- pr fteCA) n htMS2i rbbyoine ta nl ln h ne–ue ieohr xs(a et (Wan axis kinetochore inner–outer the along angle an at oriented probably is MIS12 that and CCAN), the of (part CENP-I of outside nm 15 Inner end 0 motieo EPA hc sbudt h etoee(o eitd,adaot6 motieo EPIwti MT-bound within CENP-I of outside nm 65 about and depicted), (not centromere the to bound is which CENP-A, of outside nm 100 mro ihmttosi i1 complex Mis12 in mutations with embryos DNA Coiled-coil ZWINT NNF1 region Mis12 complex DSN1 MIS12 CCAN network 2 010203040506070 7 7 Drosophila C Mis12 complex , NSL1 Outer end 5n wyfo EPI(iois ta. 07 ervce l,21;Wne l,20) WN bto left) (bottom ZWINT 2009). al., et Wan 2010; al., et Petrovic 2007; al., et (Kiyomitsu CENP-I from away nm 15 SPC24 SPC25 n thsbeen has it and , - h oeua itiuino h opnnso h M ewr ssoni h eteo h figure the of centre the in shown is network KMN the of components the of distribution molecular The , KNL1–ZWINT complex 0n wyfo EPI n t -emnlrgo,wihi eurdfriskntcoetargeting kinetochore its for required is which region, C-terminal its and CENP-I, from away nm 40 1–4 (38–42) (11–14) /IKRRVSF S/GILK (Distance innmfromCENP-I) AurB sites Molecular distributionalongtheaxisofkMTs PP1 binding N Ndc80 complex MT binding I KI2 KI1 Ndc80 complex N (177–186) 250 Bub1 TPR a1 s1 r4adHr5 a ensont rdethe bridge al., and et to (Corbett CENP-C segregation shown centromere-localized chromosome meiotic been with normal influence Mis12 has of Hrr25, of subunit and consisting Dsn1 Lrs4 complex, Csm1, Mam1, monopolin the three yeast, heterotetrameric budding other In the V-shaped the 2009). to Glover, localization which and their (Przewloka for on kinetochore depend complex Spc105R, Mis12 the homologue, of subunits Knl1 fly the Loop (kink) 0 1500 500

(213–222) BubR1 TPR KNL1 (CASC5orblinkin) ˚ ihtelo einsriga ig.TeNtria CH N-terminal The hinge. a as serving region loop the with , h M ieohr ewr 5929 network kinetochore KMN The NUF2 NDC80 (HEC1) 832316 1833 1904 MIS12 binding CH domains binding ZWINT Coiled-coil (MT bindingdomains) region , 0n nieo h ue n fthe of end outer the of inside nm 50 N-terminal tail 2106 MT C h S1sbntat subunit NSL1 the f a hlclcoiled- -helical toi tal., et etrovic MT-binding ne end inner l -terminal 2009). , hore. re et e Journal of Cell Science ta. 09.I gemn iharl o N1i the undergo in cells these KNL1 that revealed for (Kiyomitsu has imaging depletion role Live be KNL1 2007). a to al., after found et are with kinetochores proteins from both agreement BUBR1, displaced Schittenhelm and In 2007; BUB1 of al., 2009). recruitment et al., Kiyomitsu that missegregation 2008; et cells chromosome al., and sister et exhibit kMTs, (Cheeseman often stable anaphase forming enter in compromised Mad1, severely Cdc20, 2012). al., complex, et checkpoint Krenn Bub3; signal mitotic and SAC together BubR1 kinetochore the brings the of that BUBR1, generate scaffold help with (assembly to a interact BUBR1 as to and serves BUB1 BUB1 KNL1 of instead that but ability suggesting kinetochore, does the the BUB1 to influence of BUB1 interaction motif might of TPR the targeting the the that and 2012). control KNL1 demonstrated al., not of et also motif KI Krenn has the 2011; studies between al., (Bolanos- these et cells of Kiyomitsu human One important 2011; in are al., interact activity and et BUB1 KNL1 SAC Garcia and normal of BUBR1 maintaining region of for N-terminal domains ( TPR the motifs the 2008; in KI with the long), al., called acids motifs, et studies amino helical other (Cheeseman and that crystallographic revealed BUB1B) X-ray have 2007). as al., et known Kiyomitsu and BUB1 (also proteins checkpoint BUBR1 mitotic partner the several and binding of CENP-F its recruitment ZWINT, the including in proteins, role kinetochore a have outer-domain to shown been has KNL1 Mis12 KNL1 the by kinetochores to large 2). a recruited (Fig. in is is complex KNL1 as Spc105R that Human and known 2010). protein yeast al., (also 300-kDa et in (Petrovic KNL1 Spc105 ZWINT of humans, with fly) in heterodimer blinkin a or is CASC5 complex in Knl1 The DNA complex centromeric Knl1 network. The inner CCAN the the of proteins to to the with the region KNL1 association connect to and kinetochore is two complex this complex other outer of the function Ndc80 main target The properly the kinetochores. to components, required is MT-binding that network KMN MT- in changes Dsn1 dramatic of towards activity. phosphorylation network binding the KMN that the 2010). evidence sensitizes al., provides et the (Welburn study reduces network This that KMN phosphorylation the of Knl1 kinase affinity and B MT-binding complex has Aurora Mis12 study for the recent of targets subunit A are Dsn1 2010). the al., that is shown et Nsl1 also to (Petrovic binding nature their that in and Nsl1 competitive of the C-terminal bind the to or in shown Spc24 site been the same have complex and Ndc80 HP1 the both of kinetochore subunits as improper Spc25 complex, to Ndc80 attributed the of be recruitment could the by HP1 observed inner defects of mitotic the perturbation the of of many Obuse However, 2007; formation 2004). al., al., the et et Kiyomitsu 2010; for al., important et (Kiyomitsu kinetochore is and the HP1, association that protein this heterochromatic found that the have chaperone with studies interacts the Several subunit Nsl1 2010). require Kaplan, kinetochores to to and targeting shown (Davies appropriate and higher been its for in CENP-A also Hsp90–Sgt1 exists complex centromere-proximal has complex similar to Mis12 a CCAN, addition if known In not vertebrates. is it but 2010), 5930 ua ioi el hthv endpee fKL are KNL1 of depleted been have that cells mitotic Human the of component key a is complex Mis12 the summary, In ora fCl cec 2 (24) 125 Science Cell of Journal , 10–12 motn o h erimn fpoenpopaae1(P)to (PP1) 1 phosphatase protein of recruitment the for important of 2012). N-terminus basic al., extreme a et the (Espeut at to residues protein MT down acid the for narrowed amino required nine were Even of are sequences stretch 1–500 activation. crucial positions the checkpoint at binding, acids persistent amino and the though onset anaphase in ihteohrcnttet fteKNntok N1also KNL1 SAC. network, the silencing KMN and the attachment kMT of in roles constituents important concert serves other BUB1 In complex. proteins the RZZ the SAC kinetochore with proteins, possibly, the and for CENP-F kinetochore ZWINT, BUBR1, partner and outer-domain required binding other is its including several that of protein targeting PP1 scaffold Knl1-recruited functional of activity 2012). phosphatase al., et the (London is Mps1 by of activity these phosphorylation of opposed this One that 2012). suggests al., also et the Yamagishi al., studies of 2012; et al., recruitment (London et the and Shepperd kinetochores for 2012; kinase to homologue responsible three checkpoint complex is Knl1 (Mph1) checkpoint turn recently, Bub1–Bub3 Mps1 yeast in checkpoint the activity More the for this the that target that SAC. a shown to is the Spc105 have of information kMT studies of silencing this separate sensor for a relays as the machinery acts MT- and KNL1 its to of proposes of attachment activity an further PP1 MT-binding study that in This the 2012). to of activity that al., manner et SAC (Espeut recruitment additive activity to binding possibly contributes recent the and A also that independent 2010). KNL1 al., by al., suggested et et kinetochore Welburn has Meadows 2011; chromosome 2010; KMN al., study al., accurate et the et Rosenberg in (Liu of 2011; within alignment assists destabilization sites and the consequently biorientation multiple in and involved phosphorylating network), the is (by of which activity kMTs B, the counteracts Aurora activity kinase PP1 kinetochores. outer uhr xrse uatKL1ta akdteMT-binding the of lacked aspects that the KNL-1 study, in other activity mutant that the In a and 2012). for expressed al., attachments authors dispensable et but kMT (Espeut segregation activity proper in chromosome SAC shown of for been al., necessary has formation et it 2008; is and (Cheeseman this al., 2012), N-terminus that al., et extreme MT- et have Espeut its (Cheeseman to 2006; shown at been KNL1 also activity has of binding KNL1 2007). function in al., et However, the Kiyomitsu 2008). appear not require al., does kinetochores et to to Gassmann recruitment NDC80 2009; complex cells, al., human Ndc80 et the recruiting Essex in 2008; in KNL-1 role Apart complex checkpoint kinetochore, a 2007). RZZ the the have al., and to to et shown BUBR1 been (Kiyomitsu and has anaphase BUB1 of recruiting onset from the decondensation to chromosome premature prior and mitosis accelerated oo opee ocekon rtissc steMAD1–MAD2 the as such dynein–dynactin proteins and the checkpoint the attach to KNTC1) recruits to complexes turn motor as serves in that known of Spindly complex protein RZZ (also part adaptor The ROD is 2005). (Karess, proteins ZW10 ZWILCH two 2). also (Fig. which the complex, 2000) RZZ contains the al., complex, kinetochore et outer ZW10 another of (Starr targeting the kinetochores in implicated to been has initially that protein in (KBP-5 ZWINT ZWINT h xrm -emnso N1hsas ensont be to shown been also has KNL1 of N-terminus extreme The nsmay N1i ag ut-oanadmulti- and multi-domain large a is KNL1 summary, In .elegans C. .elegans C. mro,adfudta hyehbtdelays exhibit they that found and embryos, sa27aioai kinetochore 277-amino-acid a is ) .elegans C. Cesmne al., et (Cheeseman .elegans C. Journal of Cell Science 04 ose l,20) eety WN,woesrcuehas structure whose ZWINT, Recently, 2005). not al., al., but et et Cheeseman network, 2006; Kops al., KMN 2004; et the (Cheeseman complex of found RZZ components was the with ZWINT the Surprisingly, with Lin 2004), co-purify 2005; al., al., to et et Wang kinetochores (Kops 2006; to studies al., complex et for subsequent RZZ in role confirmed the A been of 2007). has al., recruitment et the Griffis in 2008; ZWINT al., et (Gassmann complex uoaBtre ie ihnteNtria alo NDC80 demonstrated and been of Santaguida has It tail 2006; 2007). al., al., N-terminal et et the Wei DeLuca 2009; 2006; within Musacchio, al., 2011). sites et al., nine the et target (Cheeseman monomers of Tooley B phosphorylation tubulin 2008; by al., Aurora weakened of et are C- Ciferri interactions E-hooks) charged 2010; These negatively so-called al., et the (the (Alushin with tails interact 2011). of to al., tail terminal required N-terminal et the is Tooley that demonstrated NDC80 2011; been al., has for timely it et required Furthermore, and NUF2, (Sundin is force progression of functions, kinetochore mitotic these MT-dependent domain for normal CH non-essential for producing is and the it attachments whereas kMT although are stable tail alignment, of N-terminal charged chromosome formation its the that and for suggest domain important mitosis CH during NDC80 complex the both Ndc80 the DSN1 within and domains NSL1 and humans the in with complex or above). Mis12 in C- (see 2012), the al., The CENP-T et al., of (Bock 2007). components et yeast both al., budding Schleiffer and with et 2011) 2012; al., Wei interacts et 2008; (Gascoigne SPC24–SPC25 humans al., of et terminus and Ciferri (Cheeseman dimer 2008; dimer NDC80–NUF2 SPC24–SPC25 Desai, the the overlapping of of N-terminus C-terminus by the and the together at SPC25, located held and Ndc80 domains SPC24 are and The NUF2, and complex. that of (HEC1) recent consisting NDC80 this complex dimers, the heterotetrameric of two 57-nm-long summarize a understanding to is this our complex attempt and in only 2012), advances thus Fukagawa, will and Commentary and Takeuchi Lampert 2010; 2011; 2011; al., Nogales, et Westermann, Joglekar and 2012; Alushin and Musacchio, (see structure and complex DeLuca the Ndc80 discussed the have of reviews function extensive of number A complex Ndc80 The a homologue recently, KNL1 2012). yeast al., the Very et for (Jakopec partner 2011). Spc105 in binding a identified al., as been this yeast has RZZ et ZWINT fission of that Kasuboski homologue the functional 2007; proposed potential is of turn Chan, (Famulski been in signaling which SAC and recruitment and has kinetochores, motility to chromosome for for motor It important phosphorylation dynein the for required kinase. and the substrate complex B is a of 2008). Aurora be phosphorylation al., to component the et known stable its by (Famulski also in is a kinetochores dynamic more ZWINT metaphase is is at complex also RZZ ZWINT residency has the the it whereas that of 2009), kinetochore, constituents shown Musacchio, other of and the been to reports (Santaguida Similar network 2011). explain al., 2004) KMN et al., (Lin al., et might complex Ndc80 et Vos the KNL1 this of 2006; (Obuse subunit MIS12 (HEC1) of and NDC80 tight and the and domain ZWINT 2010), a between coiled-coil form al., interactions C-terminal to et the demonstrated (Petrovic been with has complex motives, coiled-coil tde hthv nlzdtevrospeitdMT-binding predicted various the analyzed have that Studies a hlclcie coil coiled -helical Drosophila in hc locnan Hdmi,i o novdi the in involved 2010; of not al., et is ends Alushin 2011; domain, al., the et CH (Sundin NUF2, a MTs subunit at with Ndc80 contains interaction the that study also protofilaments found al. have et which studies Alushin curled other The two affinity. and low to with high the MTs with enables depolymerizing protofilaments and that MT straight conformation ‘toe’ to The tubulin affinity bind print’. the to ‘toe of complex termed sensor Ndc80 site a a within at as located 2008; NDC80 serves is of al., region domain MT-binding et CH key (Wilson-Kubalek the A 2010). complex al., et Ndc80 Alushin the by binding (Umbreit complex 2012). B Ndc80 al., Aurora the et of of importance function the the are for emphasizing complex phosphorylation further the so, of do al., to versions MTs, unable phosphomimetic depolymerizing track, et of B can ends Aurora Welburn the beads whereas of to 2006; 2006; rescue promote bound and al., al., preparations NDC80 stabilize chromosome dephosphorylated et protein et that mitotic reconstituted Sandall show Cimini with of 2006; Studies 2006; fidelity al., 2010). al., et the et DeLuca for (Cheeseman relevant segregation which errors, highly MT-attachment of is correction and attachment kMT vivo idMs hshrlto fkyaioai eiusa h N- the MT-binding influences at negatively residues kinase B acid Aurora to amino by subunit tail key terminal NDC80 of its Phosphorylation of MTs. domains the bind tail both and uses domain to and CH kinetochores N-terminal at interface vertebrates) 2010). MT-binding major al., the et in for Maciejowski al., essential 2010; et TTK al., Hewitt is 2004; et al., which Santaguida et as (Vigneron 2010; checkpoint activation, anaphase prevent the known to its SAC of the to been (also recruitment also leading of the have kinetochores, MPS1 for B with Aurora important Phosphorylation kinase by be onset complex to Ndc80 segregation. anaphase shown the to and MAD1–MAD2 premature chromosome NDC80 recruit exhibit to of unable erroneous and mutation are 165 non-phosphorylatable kinetochores serine a CH al., at et expressing NDC80 NDC80 (Wei SAC the Cells the phosphorylation and within this 2011). alignment and chromosome 165 NEK2, Miller for kinase serine important the 2002, is for addition, al., target a In et is domain 2008). Martin-Lluesma al., 2008, et complex al., MAD1–MAD2 et the as (Guimaraes such proteins checkpoint spindle Ndc80 Ndc80 neighboring the with of and interaction monomers the complexes. tune tubulin fine with an to complex two with the serves the at interface at sites one phosphorylation the different complex; region, at Ndc80 tail other MT-bound the the adjacent organized in and are zones sites interface or B tubulin-binding segments Aurora separate that shows two (Alushin study as detail This more domain 2012). even tail al., in the clustering et Ndc80 of al., and role et (Cheeseman binding Tooley the MT 2009; dissected studies in tethering al., the study et other recent Powers 2008; Another in several al., that 2011). et idea by Ciferri aids an 2006; supported al., evidence binding, et been NDC80 MT has upon provide 2008). of complexes that al., Ndc80 al. tail et adjacent together (Ciferri N-terminal et MTs the to unstructured with Alushin complex interfere Ndc80 domain Additionally, the CH NUF2 of showing the binding report within previous a mutations despite that 2008), al., et Wilson-Kubalek tutrlsuishv rvddipratdtiso MT of details important provided have studies Structural ae oehr h eeoermrcNc0cmlxeegsas emerges complex Ndc80 heterotetrameric the together, Taken recruiting for important also is NDC80 of domain CH The htArr iaeatvt sipratfrdestabilizing for important is activity kinase B Aurora that h M ieohr ewr 5931 network kinetochore KMN The nvitro in Journal of Cell Science uayts u eetsuisaebgnigt hdlgton higher light shed in to discovered beginning are been studies not recent but Dam/Dash have eukaryotes, the of components homologs kinase, complex Structural B Lampert 2011). 2008; Aurora al., Westermann, et of Grishchuk and 2011, homologue Nogales, yeast and a (Alushin also the Ndc80 Ipl1 is the for and MTs, of target depolymerizing processivity to prominent attached the is Dam/ increase it 2011). to when complex Westermann, shown and been spirals has (Lampert open Dash or lattice structures MT Dam/Dash ring-like the stable around The oligomers closed into either kinetochores. assemble form that subunits and to 10 Ndc80 of MT- localization composed kinetochore-bound a is kMT complex its the is complex) on effective for Dash depends complex for the that as required protein known yeast, binding (also are In complex 2010). al., Dam and et the (Joglekar network generation force complex and Ndc80 KMN attachments the with the interact to potentially or coupled that is plus- MAPS network kMT by pivotal of KMN ends dynamics the the depolymerization address of and to polymerization activity the been the has how of research question of area active complexes Another MAP Ska function in and network Dam/Dash role KMN into a insights Further plays kinetochores. also to Mps1 domain the and error MAD2 CH attachment regulate MAD1, of recruiting N-terminal to process mechanism The the and effective correction. attachment an kMT of as strength serves and affinity 5932 K3adteetr K2 hc sas opeeyhlcl hs eia tutrsitrc ihec te ttosprt ein ofr two form to regions separate two at and other SKA1 each of with domains interact helical structures N-terminal helical the These of figure). helical. consists the sites completely monomer MT-binding of also Ska four is the panel which of possess lower SKA2, core to (see entire structural envisaged subunits The the be SKA3. and SKA3 and SKA3 can and SKA2 complex SKA1 between this interaction the and the in bridge subunits, each SKA3 one and figure), SKA2 the SKA1, of the panel of upper each (see of copies two of consisting fisatcmn oMs(earks ta. 02.Amjrfnigo htsuyi htteSacmlxi a is complex Ska the that is study that basis molecular of the finding into major light sheds A which 2012). solved, al., recently been et has (Jeyaprakash complex MTs Ska to human complex the attachment of Ska its domains the of dimerization the of of structure structure crystal the The from insights Further 1. Box h rsa tutr ftedmrzto oano h k ope ugssta h K1sbntfntosa tutrlfaeokto framework structural a as functions subunit SKA1 the that suggests complex Ska the of domain dimerization the of structure crystal The SKA3 ora fCl cec 2 (24) 125 Science Cell of Journal SKA1 SKA2 MT-binding SKA1 SKA3 SKA2 Δ Δ Δ C C C ~35 nm ~ 18nm tutr a idypoie yA rci earks n ln Conti Germany). Elena Martinsried, and Biochemistry, Jeyaprakash crystal of Arockia the A. Institute of by (Max-Planck diagram provided The kindly 2012). was C-terminal al., structure SKA3 C-terminal et the (Schmidt this of unclear activity within DNA- remains MT-binding domain sites of The binding. characteristic of MT phosphorylation is inhibit domain that that and structure C-terminal proteins, tertiary the recent binding winged-helix within Another site a MT-binding 2012). is SKA1 al., domain the et that determined (Jeyaprakash has arrest study mitotic in mitotic delays residues or severe key exhibit in progression core mutations dimerization have hydrophobic central or complexes the domains in Ska MT-binding containing the lack Cells either ends. that and MT attachment depolymerizing kinetochore enhance at to processivity geometry proposed lateral interaction is This complex, protofilament MTs. Ndc80 longitudinal the of the of curvature with the concert across in transversely linkage, bind to complex. it Ska help the might of dimerization sites after ‘W’ MT-binding the effective putative of four arms accomplish the two the contain of to and SKA3 ends and the SKA1 utilized from the project both are subunits of domains C-terminal central which globular the The enables interactions dimerization. form that that confirmation molecular open helices W-shaped other an key short the has each of the interface the arms longer with of dimerization two hydrophobic ends intertwine the form the form N-terminal subunits to to The of three solvent structure. the the face-to-face ends into outwards of helical interact point C-terminal each and short subunit of the the bindles the whereas helical of of interphase, ends each dimerization N-terminal from The bundles bundles. helical intertwined h uhr pclt htti rpsdgoer fteSacomplex Ska the of geometry proposed this that speculate authors The T nacoeaiemne Wlune l,20) Moreover, 2009). al., et (Welburn manner cooperative human The a 2009). in reconstituted Raaijmakers al., MTs been et 2006; Welburn has al., 2009; complex be al., et Ska et Hanisch to Theis al., 2009; 2009; et al., reported al., et (Daum et is segregation Gaitanos complex chromosome 2009; anaphase Ska SAC and alignment, al., the metaphase silencing formation, et kMT cells, (Gaitanos normal whole for human stability important a proper as In complex the 2009; Ska for 2009). the required al., of is 2009; et functioning SKA3 al., and et 2009). (Daum Theis al., 2009; SKA2 al., et et Welburn and Raaijmakers was 2009; al., SKA1 et RAMA1, Gaitanos of those to and called phenotypes knockdowns MTs, identical in spindle upon also third results and protein a this SKA3, kinetochores of to knockdown Subsequently, complex, localizes 2006). that kinetochore- the discovered al., on of dependent et is subunit (Hanisch that concentrate NDC80 to manner and a bound MTs in spindle and to kinetochores SKA1 localize at SKA2. to and found regulatory SKA1 were SKA2 these proteins two of comprising modes complex major the below. of discussed one as KMN functions complex as the Ska or emerged kinetochore-localized complex the has Ndc80 cells, the human In with network. interact that MAPs other sebista ifs ln T n hti id to binds it oligomeric that form and can MTs complex along 2012), Ska al., diffuse et the (Schmidt that data that recent assemblies more shown as well have as study, that h k ope a ntal dniidi ua el sa as cells human in identified initially was complex Ska The , 5n-ieWsae dimer, W-shaped 35-nm-wide nvitro in n hw obind to shown and Journal of Cell Science ope obn T nacoeaiemne.Teeproperties These manner. cooperative Ndc80 a the in of MTs capacity bind the complex to enhances complex straight complex MTs Ska complex. Ska Ndc80 depolymerizing the purified only purified of the Moreover, of ends tracking The plus-end the binds strengthens at and ends). motion complex processive MT exhibits Ndc80 near protofilaments (the MT curved and straight protofilaments both along plus-ends MT depolymerizing n mar t oei tblzn M attachments. kinetochores kMT to stabilizing complex in role Ska its the in impairs which of and network, recruitment KMN the the inhibits with the turn complex regulates Ska negatively the phosphorylation by of phosphorylation their association for that targets and are B SKA3 also Aurora study and That SKA1 2012). al., that et showed (Chan network three KMN all the on depends of kinetochores complex, members to Ndc80 Ska the of recruitment to the addition that in and complex, Mis12 the and KNL1 al., et Welburn 2012). not 2006; al., al., possibly et et Schmidt Hanisch (but 2009; 2009; functional al., in et complex a (Gaitanos Dam/Dash the yeast be of vertebrates could in suggests homologue complex and structural) kinetochores, MTs Ska to of the localization requirement its that the for with complex Ndc80 together the complex, Ska the of Msrqie As uha i1(iso es) h a/ahcmlx(udn es) rpsil h k ope hmncls.In cells). (human We complex below). (see Ska attachment the kMT robust to possibly for domain required or loop is addition, yeast), and the In region (budding from MTs. loop Linkage complex the to is indirectly. to bind Dam/Dash binds albeit (HEC1) KNL1 also the complex, confirmation. of NDC80 CDT1 Ndc80 yeast), complex N-terminus protein of licensing the extreme (fission in replication within the domain flexibility DNA Dis1 site and the provides loop as red) MT-binding cells, that human the in third such region shown a that MAPs, figure, loop provides found requires (see located NDC80 NDC80 kMTs have of centrally of of region a attachment lines tail loop Several with N-terminal kMT 2012). central bent the Stukenberg, the in and and slightly Matson domain network is 2012; CH al., complex KMN the et Ndc80 Varma Both the 2012; the of al., that et role (Zhang suggest figure) evidence the (see attachments on kMTs stabilizing cells in domain instrumental human loop in NDC80 studies human Recent the of Function 2. Box hr sas vdneta h k ope neat with interacts complex Ska the that evidence also is There Key CENP-A Human KMNnetworkandtheNdc80loop-interacting complex(Ska) MAPs bindingtheloopinyeast(e.g.Dis1 andDam1) Human NDC80loop-bindingprotein,CDT1 CENP-T CENP-C (View normaltotheaxisofkMT) Mis12 complex KNL1 NDC80 loopmotif Ndc80 complex o bev infcn eraei h ocnrto fteSka the mutated. was of region concentration loop the NDC80 the in when decrease kinetochores at did significant study complex our a Intriguingly, an observe attachments. kMTs, maintain kMT not of robust to presence more the in helps in aids complex which NDC80 to Ndc80 CDT1 the kinetochore-bound of of confirmation of binding extended the region that loop suggests and the of complex 2012) the analysis Ndc80 al., NDC80, Detailed 2012). et the al., (Zhang of et is of missing to structure (Varma that is inhibited is region loop arrest CDT1 CDT1 the when mitotic when or loop of a observed induces that the localization sequence to similar kMT region The on loop SAC- in the 2012). dependent scrambling or defects a al., is severe approaches et kinetochores induces with RNA-based (Varma arrest antibodies attachments prometaphase interfering function-blocking late small dependent of either interacts microinjection during by specifically that function protein CDT1 to of kinetochore mitosis replication Inhibition novel complex. DNA attachments Ndc80 kMT a the the of with as identified MT stabilization CDT1 We the protein 2012). in for licensing by al., study, mechanism et Ska defects second new (Varma A loop-recruited a attachments mutations. observed presented the loop group, with the our of cells mitotic absence to in kinetochores the led that complex Ska complex and the recruits kinetochores, directly are domain the region 2012). to loop al., are the loop that et that (Zhang the complex that found proposed Ska of They the al. proteins with absence properly et associate the other to Zhang in unable of assembled attachments. recruitment complexes kMT Ndc80 the normal for for required important is region figure. the the within in positions accurately relative depicted their not and are kMTs, kinetochore of to orientation and relative location proteins exact these the about knowledge limited have only on ob vltoaiycnevdfo es ohuman to yeast from site conserved was this loop evolutionarily at the be encompassing structure sequence secondary to in The the break found 2008). which in al., a NDC80, et loop with within (Wang a region coincides produces coiled-coil kink central likely the the of of Ndc80 the registry location of structure The the NDC80. in bend or kink complex prominent domain a loop is NDC80 There the of role The a egie rmteSasrcueaepeetdi o 1. Box in presented are structure Ska the the that from insights preventing gained Further Also for been be cohesion. 2009), can has chromatid al., resolved. sister et as of (Daum loss being such al. premature et Ska progression, from Daum the mitotic by for far proposed controlling activities additional in are are complex there function whether lattice MT is this the unresolved and network fulfill KMN details the finer to with the associates but Ska Recent functional complex, how B. vertebrate Dam/Dash of a yeast Aurora kMT indeed the is of to by Ska homologue stability that phosphorylated indicates provide is also evidence to it and particular, network, unless KMN in attachments the complex of components Ndc80 the the with concert close in eunemdfctosi h oprgo aesonta this that shown have region loop the in modifications Sequence ae oehr hs tde hwta h k ope works complex Ska the that show studies these together, Taken , 6n wyfo h TbnigC oanof domain CH MT-binding the from away nm 16 h M ieohr ewr 5933 network kinetochore KMN The Journal of Cell Science k ope side notoou fDmDs n how and Dam/Dash of it. orthologue with an the interact if indeed understand that to is proteins us help complex the will Ska direction for and this in chance complex loop efforts high the Research Ndc80 of a and function the the is SAC of there the study in further in which the is role in progress its area, immediate of An is information attachment. region this valuable kMT of yield its analysis Knl1, and to of box’ likely C-termini ‘black the a to and remains know N- region we the central Although of worthwhile. functions be the extent to some likely research more is and direction its slow this of relatively in control been understanding has our a and function is and in Knl1 structure SAC progress As protein, PP1. and and multi-domain MPS1 large attachment B, Aurora MT by of governed intricacies mechanisms between the elucidate al., interplay to et mandatory (Espeut the is activity work checkpoint more to controlling but shown likely for 2012), is slowly as sensor Knl1 by key mechanisms MT-binding are a that these be suggests that We of work recent some by difficult. understand their to exceedingly makes beginning which analysis transient, the highly with biochemical the possibly proteins checkpoint are into of problem network association back the the KMN that of feeds fact Part the checkpoint network. in KMN lies the dynein- the how of trigger machinery or attachment checkpoint, attachments silencing the and MT (‘stripping’) of components how SAC of removal lack of the mediated still for we knowledge However, prerequisite the 3). a recruit (Fig. precise be MAD2 complex to and MAD1 Ndc80 appears of turn the recruitment in and which ZWINT complex, Both RZZ 2008). al., et U1 swl steRZcmlxin complex and RZZ BUBR1 the ZWINT, as recruiting SAC MAD1, well for recruiting required as the in is know involved BUB1, and already is KNL1 NDC80 We that of RZZ). network and domain the CH and KMN the Bubs that the the the Mads, between the connections of (including the components delineate to different help will work directions Future future and remarks MT- Concluding different complex. three Ndc80 of the total within a domains MT- providing binding a and constitutes thus domain also CH interface, domain the loop binding to its addition NDC80, in of tail that N-terminal notion the support 2), Box of complex. targeting artificial Ndc80 the the by to rescued Dis1 was and 2011). mutations mitotic loop prolonged the Toda, with cells undergo of and they in Deletion and activated (Hsu arrest. domains persistently loop ends mutated remains MT with SAC the spindle the end- of to Consequently, stable recruitment with attachments the kinetochores region, to for loop on XMAP215) important or the (TOG is within Dis1 region MAP sequences this or that and residues showed yeast key attachments fission of the kMT mutation in end-on) pombe study of other Saccharomyces conversion (i.e. The the bi-orientation. in load-bearing defect kinetochore severe to (Maure a is kMTs is to region lateral there loop to the complex mutated, when on or that, Dam/Dash in observed loading deleted authors Those its the study, 2011). al., for of et first possibly recruitment and The the kinetochores attachment. for important kMT cerevisiae stable Saccharomyces for important not was function its recently very until but clear. 2008), al., et (Wang 5934 hs tde,aogwt eetsuisi ua el (see cells human in studies recent with along studies, These is region loop the that determined yeast in studies Two ora fCl cec 2 (24) 125 Science Cell of Journal hc louigdlto rdirected or deletion using also which , Dis1 hwdta h oprgo is region loop the that showed , eepeooistedfcsseen defects the phenocopies gene .elegans C. (Gassmann lcdt hte ifrn d8 opbnigpoen c in also attachments. act and kMT stable 2), proteins accomplish Box loop-binding to (see Ndc80 concert kMTs different of of change whether presence conformational elucidate the the in licensing influence complex replication to the Ndc80 able on the is light which CDT1 shed by also protein and mechanism should studies molecular correction Future exact error SAC. the attachment kMT of coordinate control generation, network KMN force the and attachment, complex Ska the exactly i.3 oeo h M ewr nteSAC. the in network KMN the of Role 3. Fig. ealdtefnto fteNc0lo oan(iso,2012). (Nilsson, domain journal loop Ndc80 the Jakob the by of in written function review the published a detailed manuscript, was this of Nilsson acceptance the After proof in added Note months. E.D.S.]. 12 to after release supplement for of and PMC Institutes in R37GM024364 National the Deposited number by supported [grant is laboratory Health our of work The the Funding of members Jean present discussions. thank and insightful to past for laboratory several like Ska Salmon and also the Deluca, would of Jenifer structure We Elena Cook, high-resolution and domains. the Jeyaprakash dimerization with Arochia complex us A. providing acknowledge for to Conti like would We Acknowledgements silencing. dynein details. SAC the for during for text complexes required See checkpoint is these and of complex complexes, stripping motor RZZ motor-driven dynein–dynactin and the MAD1–MAD2 RZZ between the the adaptor and by an (recruited as Spindly serves complex. ZWINT complex) checkpoint of recruitment BUB1–BUBR1 kinetochore the MAD1– the in and the for unattached important of are is localization that KNL1 proper kinetochores prometaphase. the to for complex required checkpoint complex be MAD2 RZZ to the and shown complex been Ndc80 have the Both complex. arrows). checkpoint by RZZ (indicated the other in KNL-1 each and of (KBP-5) of recruitment ZWINT recruitment their the and in (red) components proteins network SAC KMN of function known the shows .elegans C. r eurdfrtercutetof recruitment the for required are Bioessays h ceai illustration schematic The eciigin describing , Journal of Cell Science ohm,G n aaia M. Yanagida, and G. Goshima, asan . se,A,H,J . adx .S,Mtg,F,Sgmt,A., Sugimoto, F., Motegi, S., P. Maddox, S., J. Hu, A., Essex, R., Gassmann, Cheeseman, and T. Fukagawa, T., Hori, A., Suzuki, K., Takeuchi, E., K. Gascoigne, ais .E n aln .B. K. Kaplan, and E. A. Davies, acin,K .adCesmn .M. I. Cheeseman, and E. K. Gascoigne, am .R,We,J . ail .J,Svkmr . cvy .N,Potapova, N., J. McAvoy, S., Sivakumar, J., J. Daniel, D., J. Wren, C. R., S. J. Harrison, and Daum, A. Amon, T., Walz, S., L. Ee, K., C. Yip, D., K. Corbett, D. E. Salmon, and B. C. Hirel, X., Wan, D., Cimini, G., Reis, Dos S., Santaguida, G., Varetti, E., Screpanti, S., A. Pasqualato, C., Desai, Ciferri, and T. Fukagawa, T., Hori, M., I. Cheeseman, A. Desai, and M. E. Wilson-Kubalek, S., J. Chappie, M., I. Cheeseman, A. Desai, and M. I. Cheeseman, atns .N,Snaai,A,Jypaah .A,Wn,B,Cni .adNigg, and E. Conti, B., Wang, A., A. Jeyaprakash, A., Santamaria, N., T. Gaitanos, heea,I . ise,S,Adro,S,Hnmn . ae,J . 3rd, R., J. Yates, F., Hyndman, S., Anderson, S., Niessen, M., I. Cheeseman, A. Santamaria, and A. E. Nigg, A., A. Jeyaprakash, W., Y. Chan, ot,D . asn .E,Bak .E,Bie,A . ae,J . r and 3rd R., J. Yates, O., A. Bailey, E., B. Black, E., L. Jansen, R., D. G. Foltz, Chan, and X. Sun, L., Vos, K., J. Famulski, K. G. Chan, and K. J. Famulski, oao-aca .M,Lshti . Matak-Vinkovic T., Lischetti, M., V. Bolanos-Garcia, Alfieri, K., Shrestha, Y., Oku, and A., R. T. Grove, N., P. Kobayashi, C., Stukenberg, Pagliuca, J., J., L. Bock, Tooley, D., Matson, V., Musinipally, M., G. Alushin, se,A,Dmemn,A,Lwly,L,Ogm,K n ea,A. Desai, and K. Oegema, L., Lewellyn, A., Dammermann, A., Essex, A. Desai, and K. Oegema, L., Krenning, K., D. Cheerambathur, J., Espeut, lsi,G . ae,V . aqaao . al .A,Gioif,N,Musacchio, N., Grigorieff, A., D. Ball, S., Pasqualato, H., V. Ramey, M., G. Alushin, eua .G,Gl,W . ier,C,Cmn,D,Mscho .adSlo,E D. E. Salmon, and A. Musacchio, D., Cimini, C., Ciferri, E., W. Gall, G., J. DeLuca, A. Musacchio, and G. J. DeLuca, lsi,G n oae,E. Nogales, and G. Alushin, References rccossprto ftesse ieohrs u o h rs nteeryspindle early the in arms, the not yeast. but budding kinetochores, of sister the of separation precocious ftodni-agtn opnns PL1adteRdZic/w0complex. Rod/Zwilch/Zw10 the and SPDL-1 Dev. components: Genes dynein-targeting comparison al. et by two 3rd revealed of R., interactions J. kinetochore-microtubule Yates, I., controlling McLeod, mechanism B., Bowerman, M., S. O’Rourke, nucleosomes. CENP-A M. I. hywl come. will they opee oesr fiin omto fkntcoemcouuebnigsites. binding kinetochore-microtubule of formation efficient ensure to complexes mitosis. in cohesion chromosome of maintenance J. the G. and Gorbsky, and A. T. errors. segregation chromosome reduce Ndc80 Biol. to microtubules engineered kinetochore of an turnover of al. structure et P. the Wulf, De from complex. G., J. attachment Luca, De kinetochore-microtubule J., Polka, A., Maiolica, vertebrates. in assembly Cell kinetochore Biol. direct coordinately complex CENP-H/I/K n t e opnn Ska3/C13Orf3. component new its and A. E. h oooi ope rslnskntcoecmoet orglt chromosome- regulate to attachments. components microtubule kinetochore crosslinks complex monopolin The the of site microtubule-binding core the constitutes network kinetochore. KMN tension. sustain conserved to ability its and kinetochore outer the A. Desai, and K. Oegema, complex-KMN interface. microtubule Ska inhibiting by interaction. attachments network kinetochore-microtubule controls complex. W. D. Cleveland, 21) tutr faBiknBB1cmlxrvasa neato rca for crucial interaction L. an T. Site. reveals Blundell, binding and unanticipated complex 19 an J. via Blinkin-BUBR1 Nilsson, regulation V., a checkpoint kinetochore-mitotic C. of Robinson, Structure R., D. (2011). Spring, Y., D. Chirgadze, al. et M. kinetochore. Maschio, yeast the Dal of 614-624. complexes A., KMN the Oldani, between interactions C., Golfieri, C., complex. E. Nogales, eiec,mdae yhwn- neato,i seta o h ioi checkpoint. mitotic the for essential Biol. is Cell interaction, J. hZwint-1 by mediated residency, kinetochores. tensionless to hROD and hZW10 ln microtubules. along E. Nogales, and A. ytmtcaayi nCeohbii lgn eel httesidecekon is checkpoint branches. spindle independent the largely that two reveals of elegans composed the Caenorhabditis in at analysis silencing Systematic checkpoint spindle to contributes KNL-1 kinetochore. by binding Microtubule by regulated are stability attachment and Hec1. dynamics microtubule Kinetochore (2006). tut Biol. Struct. irtbl interface. microtubule Biol. Cell J. 1691-1700. , 16 20) tbekntcoemcouueitrcin eedo h k complex Ska the on depend interactions kinetochore-microtubule Stable (2009). Cell 21) nue coi ieohr sebybpse h eurmn for requirement the bypasses assembly kinetochore ectopic Induced (2011). 1711-1718. , Cell a.Cl Biol. Cell Nat. a.Src.Ml Biol. Mol. Struct. Nat. 19 127 22 21 587-594. , 180 189 Cell .Cl Biol. Cell J. 21) utmdlmcouuebnigb h d8 kinetochore Ndc80 the by binding microtubule Multimodal (2012). 2385-2399. , 133 969-982. , 661-669. , ur pn elBiol. Cell Opin. Curr. 507-520. , 261-274. , 127 Cell 427-439. , 20) h ua EPAcnrmrcnucleosome-associated centromeric CENP-A human The (2006). 21) h d8 ieohr ope om lgmrcarrays oligomeric forms complex kinetochore Ndc80 The (2010). Nature .Cl Biol. Cell J. 983-997. , a.Rv o.Cl Biol. Cell Mol. Rev. Nat. ur pn elBiol. Cell Opin. Curr. 100 Cell 8 Cell 196 458-469. , 619-633. , 20) osre rti ewr otosasml of assembly controls network protein conserved A (2004). 21) iulzn ieohr architecture. kinetochore Visualizing (2011). 20) k3i eurdfrsidecekon silencing checkpoint spindle for required is Ska3 (2009). 467 145 469-482. , 142 805-810. , 410-422. , 21) s9-g1adSp agthmnMis12 human target Skp1 and Hsp90-Sgt1 (2010). 20) oeua rhtcueo h kinetochore- the of architecture Molecular (2008). 19 20) uoaBkns-eedn erimn of recruitment kinase-dependent B Aurora (2007). 21) tutrlognzto ftekinetochore- the of organization Structural (2012). 196 556-567. , 20) salsigboinainocr with occurs biorientation Establishing (2000). 1161-1167. , 563-571. , 21) ieohr seby fyubidit, build you if assembly: Kinetochore (2011). 23 MOJ. EMBO 102-108. , 24 ur Biol. Curr. 48-56. , 9 o.Bo.Cell Biol. Mol. 20) tbehW0kinetochore hZW10 Stable (2008). 33-46. , 28 1442-1452. , ´ 20) uoakns promotes kinase Aurora (2006). . oa . ipo,P J., P. Simpson, E., Cota, D., , ee Dev. Genes ur Biol. Curr. 21) n1ihbt the inhibits Cnn1 (2012). 17 20) mlctosfor Implications (2008). 20) N1adthe and KNL1 (2008). 2143-2149. , 20 a.Cl Biol. Cell Nat. 1252-1267. , 21) uoaB Aurora (2012). 18 19 20) new A (2008). 2255-2268. , 1467-1472. , 20) The (2006). ur Opin. Curr. Structure (2010). (2009). (2012). Curr. Mol. 14 , rscu,E . feo,A . okv .A,Siioo,I . uicu,N., Gudimchuk, S., I. Spiridonov, A., V. Volkov, K., A. Efremov, L., E. Grishchuk, rfi,E . tumn .adVl,R D. R. Vale, and N. Stuurman, R., E. Griffis, ohm,G,Sio,S n aaia M. Yanagida, and S. Saitoh, G., Goshima, aijwk,J,Gog,K . ert .E,Zag . hkt .M and M. K. Shokat, C., Zhang, E., M. Terret, A., K. George, J., Maciejowski, iois,T,Iaai . bs,C n aaia M. Yanagida, and C. Obuse, O., Iwasaki, T., Kiyomitsu, odn . eo . aih .A n ign,S. Biggins, and A. J. Ranish, S., and Ceto, M. N., I. Cheeseman, London, T., Fukagawa, T., Hori, B., C. Backer, M., Vleugel, D., Liu, H. W. Lee, and G. Wu, Y., Chen, T., Y. Lin, aoe,V,Tplk,B n li,U. Fleig, and B. Topolski, V., Jakopec, iois,T,Oue .adYngd,M. Yanagida, and C. Obuse, T., Kiyomitsu, apr,F n etran S. Westermann, and F. Lampert, s,K .adTd,T. Toda, and S. K. Hsu, auok,J . ae,J . aga,P . aht,S . idn,M., Winding, B., S. Tauhata, S., P. Vaughan, R., J. Bader, M., J. Kasuboski, D. E. R. Salmon, Karess, and S. K. Bloom, P., A. D. E. Joglekar, Salmon, and K. Bloom, P., A. Joglekar, C., Benda, W., Y. Chan, U., Jayachandran, A., Santamaria, A., A. Jeyaprakash, rn,V,Whne,A,L,X,Snaud,S n uaci,A. Musacchio, and S. Santaguida, X., Li, A., Wehenkel, V., Krenn, onn,P,Mir . lsi,G . adr .C,Ngls .and E. Nogales, C., G. Lander, M., G. Alushin, M., Maier, P., Hornung, os .J,Km . evr .A,Mo . ced . ae,J . r,Tagaya, 3rd, R., J. Yates, I., McLeod, Y., Mao, A., B. Weaver, Y., Kim, J., G. Kops, V. J. Shah, A. and Desai, J. G. and Kops, T. Fukagawa, T., Hori, M., I. Cheeseman, L., S. Kline, M. Yanagida, and H. Murakami, T., Kiyomitsu, oi . mn,M,Szk,A,Bce,C . ebr,J . og . McEwen, Y., Dong, P., J. Welburn, B., C. Backer, A., Suzuki, M., Amano, T., Hori, T. A., Fukagawa, Musacchio, and D., T. C. Jones, Hori, M., A. White, S., Santaguida, A., Tighe, L., Hewitt, Sillje A., G. Hanisch, J. Deluca, and F. B. McEwen, Y., Dong, J., G. Guimaraes, 20) h a1rn id irtblssrnl nuht eapoesv swell as processive motion. a be chromosome to for enough I. coupler strongly F. energy-efficient microtubules Ataullakhanov, as and binds R. ring J. Dam1 McIntosh, The G., (2008). Barnes, D., Drubin, S., Westermann, o iecn h pnl sebycekon,rcut yent h kinetochore. the to dynein recruits checkpoint, assembly Biol. Cell spindle J. the silencing for eemndb etoeepoen i1 n i6rqie o atflchromosome faithful for required Mis6 and segregation. Mis12 proteins centromere by determined alpli .V. P. Jallepalli, 900-906. p15b p1adP1rgltsBb oaiaint kinetochores. to localization Bub1 regulates PP1 and Mps1 by Spc105 kinase. B Aurora opposes KNL1 by kinetochore A. M. Lampson, omto eurshi1,atietkntcoepoenta pcfclyrcut HP1 recruits direct specifically chromosomes. that protein human through kinetochore to trident checkpoint a hMis14, requires mitotic formation the BubR1. and and alignment Bub1 with chromosome interaction for required n W0t ieohrsfrfihu hoooesgeainadspindle and segregation chromosome faithful for kinetochores to control. ZW10 checkpoint and 1 division. cell of mechanics molecular the into rprkntcoesideatcmn nfsinyeast. fission in attachment kinetochore-spindle proper wn- sanvlArr usrt eurdfrteasml fadynein-binding a al. of et assembly K. the G. for Chan, required substrate L., kinetochores. B Vos, on Aurora W., platform novel Boggess, a V., is M. Zwint-1 Joyce, A., M. Morrissey, Biol. Cell 57-67. attachments. kinetochore-microtubule end-on by generation interface. kinetochore-microtubule the of component 274-286. key E. a Conti, complex, and A. E. Nigg, a proteins. identifies kinetochore fungal complex, of Ndc80-MIND-Spc7 family new pombe Schizosaccharomyces conserved nlssrvasfaue ftesidecekon iaeBb-ieohr subunit Bub1-kinetochore kinase checkpoint spindle interaction. the Knl1 of features reveals analysis es t1kntcoecomplex. kinetochore Mtw1 yeast S. Westermann, h uaytckntcoewt aoee cl accuracy. scale nanometer with kinetochore eukaryotic the .adCeead .W. kinetochore. D. structural Cleveland, and M. BubR1. binding and for Bub1 motif proteins consensus 1011. checkpoint a assembly reveals spindle Blinkin protein of kinetochore human of mapping otcswt etoei N opoiedsic ahast h ue kinetochore. outer al. the to et pathways K. distinct Okawa, provide Cell to E., DNA Suzuki, centromeric H., with contacts W. Shang, F., B. Res. Chromosome complex. core Mad1-C-Mad2 the to O-Mad2 S. recruit S. Taylor, and S. Ska2. Green, and Ska1 comprising complex kinetochore 5504-5515. and spindle novel 15423-15428. tahetslne h pnl sebycheckpoint. assembly spindle the silences attachment chromosome proper and assembly kinetochore for required segregation. is complex Mis12 human irtbl tahetrle ntedsree -emnlti oano Hec1. of domain tail N-terminal disordered the Biol. on Curr. relies attachment microtubule 135 1039-1052. , 20) o-w0Zic:akypae ntesidecheckpoint. spindle the in player key a Rod-Zw10-Zwilch: (2005). 15 18 ee Dev. Genes .Cl Biol. Cell J. 386-392. , 177 1778-1784. , ,H .adNg,E A. E. Nigg, and H. H. ´, 1005-1015. , 21) p1drcsteasml fCc0ihbtr complexes inhibitory Cdc20 of assembly the directs Mps1 (2010). .Cl Biol. Cell J. 21) euae agtn fpoenpopaae1t h outer the to 1 phosphatase protein of targeting Regulated (2010). 21) oeua rhtcueadcnetvt ftebudding the of connectivity and architecture Molecular (2011). 20 h M ieohr ewr 5935 network kinetochore KMN The Oncogene 547-561. , 21) d8 nenllo neat ihDs/O oensure to Dis1/TOG with interacts loop internal Ndc80 (2011). .Cl Biol. Cell J. 13 .Cl Biol. Cell J. 173 o.Bo.Cell Biol. Mol. 21) oncigu n laigot o kinetochore how out: clearing and up Connecting (2012). 1664-1677. , 21) tutrladfntoa raiaino h Ska the of organization functional and Structural (2012). 20) W0lnsmttccekon inln othe to signaling checkpoint mitotic links ZW10 (2005). 21) utie p1atvt srqie nmtssto mitosis in required is activity Mps1 Sustained (2010). 21) salsmn ftevrert kinetochores. vertebrate the of Establishment (2012). 9-17. , 196 25 21) lern o ieohrs-nwinsights new - kinetochores for blueprint A (2011). 6901-6914. , 451-467. , .Ml Biol. Mol. J. e.Cell Dev. 169 188 49-60. , 21) o7 nesnilcmoeto the of component essential an Sos7, (2012). 791-807. , 19) rprmtpaesidelnt is length spindle metaphase Proper (1999). 22 20) ieyaahs ne eursa requires onset anaphase Timely (2006). 20) e1sqetal erisZwint- recruits sequentially Hec1 (2006). 20) pnl,anvlpoenessential protein novel a Spindly, (2007). o.Cl.Biol. Cell. Mol. 3318-3330. , 13 20) nvv rti rhtcueof architecture protein vivo In (2009). a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 20) ua lni/F51 is Blinkin/AF15q14 Human (2007). 663-676. , 405 .Cl Biol. Cell J. 21) rti neato domain interaction Protein (2011). 548-559. , rc al cd c.USA Sci. Acad. Natl. Proc. .Cl Biol. Cell J. 20) CNmksmultiple makes CCAN (2008). 21) ehnsso force of Mechanisms (2010). Chromosoma 21) hshrglto of Phosphoregulation (2012). ur Biol. Curr. 21) ne centromere Inner (2010). ur pn elBiol. Cell Opin. Curr. ur Biol. Curr. o.Cl.Biol. Cell. Mol. 32 188 3308-3320. , 20) Kinetochore- (2008). 809-820. , 190 21) Structural (2012). 21 121 214-220. , 25-34. , ur Biol. Curr. MOJ. EMBO o.Cell Mol. 19 509-525. , 12 20) The (2006). 694-699. , 407-412. , 31 (2011). Trends 998- , 105 22 22 46 25 , , , , , Journal of Cell Science citnem .B,Caeks .adLhe,C F. C. Lehner, and R. Chaleckis, B., R. Schittenhelm, clifr . ae,M,Lts . apr,F,Hrug . ehlr .and K. Mechtler, P., Hornung, F., Lampert, G., Litos, M., Maier, A., Schleiffer, Mechtler, S., Heidmann, A., Walter, F., Althoff, S., Heeger, B., R. Schittenhelm, atgia . ih,A,DAie .M,Tyo,S .adMscho A. Musacchio, and S. S. Taylor, M., A. D’Alise, A., Tighe, S., Santaguida, adl,S,Svrn . ced .X,Yts .R,3d eea . Hyman, K., A. Oegema, Musacchio, 3rd, and R., S. J. Santaguida, Yates, X., I. McLeod, F., Severin, S., Sandall, ath . oke,J,Coe .A,Rti,H,3d arr . ohil,N F. N. Rothfield, M., Maurer, 3rd, H., Ratrie, A., C. Cooke, J., Tomkiel, H., Saitoh, oebr,J . rs,F .adFnbk,H. Funabiki, and R. F. Cross, S., J. Rosenberg, aimkr,J . aebu,M . aa .F n eea .H. R. Medema, and F. A. Maia, E., M. Tanenbaum, A., J. Raaijmakers, M. D. Glover, and R. M. Przewloka, J. Nilsson, D. E. Salmon, and A. Musacchio, R. M. Singleton, and W. X. Hu, P., D. Maskell, A. E. Nigg, and M. V. Stucke, S., Martin-Lluesma, D. E. Salmon, and J. T. Maresca, 5936 ilr .A,Jhsn .L n tkneg .T. P. Stukenberg, and L. M. Johnson, A., S. Miller, M., A. Sochaj, C., T. Lancaster, V., Vanoosthuyse, A., L. Shepperd, C., J. Meadows, Clayton, K., Natsume, S., Pasqualato, A., Mino, Y., Oku, S., Komoto, F., J. T. Maure, P. Stukenberg, and R. D. Matson, relk,M . eki . oao-aca .M,Dbk,J,Dde,M and M. Dadlez, J., Debski, M., V. Bolanos-Garcia, Z., Venkei, R., M. Przewloka, R., R. Wei, B., Gracyzk, J., Cooper, R., Cittaro, D. Gestaut, S., D., A. Santaguida, Franck, F., V., A. Powers, Krenn, P., Dube, S., Pasqualato, A., Petrovic, T. Fukagawa, and M. Perpelescu, 3rd, R., J. Yates, X., I. McLeod, K., Okawa, Yanagida, T., Hori, and M., I. Y. Cheeseman, M., Toyoda, Okada, G., Oyama, Goshima, T., T., Kiyomitsu, Hori, O., Iwasaki, A., C., Suzuki, Obuse, E., K. Gascoigne, K., Takeuchi, T., Nishino, d8 complex. Ndc80 S. Westermann, Spc105. Drosophila of domains functional 2374-2386. essential and localization chromosomes. F. Drosophila in C. network protein kinetochore Lehner, and K. iscigterl fMS ncrmsm iretto n h pnl checkpoint spindle the and biorientation chromosome in MPS1 of role the Dissecting hog h ml oeueihbtrreversine. inhibitor molecule small the through MOJ. EMBO tension. kinetochore sense to required is and A. Desai, and A. opnn ftehmninrkntcoeplate. kinetochore inner human C. the of W. component Earnshaw, and iec h pnl sebycheckpoint. assembly spindle the silence AA sanvlkntcoepoenivle nkinetochore-microtubule in involved protein kinetochore novel a attachment. is RAMA1 time. and 2270. signal. wait-anaphase a 835. into mechanics kinetochore translating ur Biol. Curr. M. D. Glover, biased relationship. distance via long tips working microtubule dynamic L. to C. attachments Asbury, diffusion. load-bearing and N. forms T. complex Davis, L., assembly. Wordeman, al. kinetochore et outer for A. hub Tarricone, interaction J., protein Biol. Keller, a is L., complex Massimiliano, MIS12 S., Monzani, D., 425-446. centromeres. into CENP-A synthesized newly Biol. of T. incorporation Fukagawa, efficient and A. Desai, Zwint-1. protein kinetochore outer and fold. M. histone-like a with structure T. chromatin Fukagawa, centromeric 487-501. and unique M. a I. forms Cheeseman, K., Morikawa, T., segregation? chromosome control Ndc80(Hec1). and microtubules on tails Biol. unstructured Curr. between interaction an require B. motors. J. kinesin-8 Millar, and Spc7 and both to 739-750. G. PP1 of K. association requires Hardwick, silencing J., G. Buttrick, end. plus microtubule dynamic U. the 21 to T. attachment Tanaka, kinetochore of and formation A. Musacchio, L., loop. a for attachments complex. MIND kinetochore yeast the of assembly Mad1/Mad2. of recruitment kinetochore and signaling checkpoint checkpoint spindle and timing phase M control to mitosis signaling. and interphase during 207-213. , 20) osre i1 etoeecmlxi ikdt eeohoai HP1 heterochromatic to linked is complex centromere Mis12 conserved A (2004). 190 8 446-457. , 21) opn no d8 o osapoenlo ttekinetochore the at loop protein a does how - Ndc80 on in Looping (2012). 835-852. , 28 a.Rv o.Cl Biol. Cell Mol. Rev. Nat. Cell .Cl Biol. Cell J. ora fCl cec 2 (24) 125 Science Cell of Journal 21 18 .Cl Sci. Cell J. 2511-2531. , 399-405. , 1785-1791. , 136 21) EPCi tutrlpafr o ieohr assembly. kinetochore for platform structural a is CENP-C (2011). a.Cl Biol. Cell Nat. 20) i1Si5cmlxcnet etoee omicrotubules to centromeres connects complex Bir1-Sli15 A (2006). 21) EPTpoen r osre etoeercposo the of receptors centromere conserved are proteins CENP-T (2012). 865-875. , 190 a.Cl Biol. Cell Nat. 122 20) pta raiaino bqioseukaryotic ubiquitous a of organization Spatial (2007). 19) EPC natatgni ceoem,i a is scleroderma, in autoantigen an CENP-C, (1992). 89-100. , 2436-2445. , 20) h EPHIcmlxi eurdfrthe for required is complex CENP-H-I The (2006). 14 20) h pnl-sebycekon nspace in checkpoint spindle-assembly The (2007). Bioessays 21) h Bso CENPs. of ABCs The (2011). 604-613. , 20) h ieadmrce fkinetochores. of miracles and life The (2009). nu e.Genet. Rev. Annu. 8 21) ecm oanwkn ftension: of kind new a to Welcome (2010). 20) h ieohr n h etoee a centromere: the and kinetochore The (2009). 379-393. , 21) d1trw kinetochore-microtubule throws Cdt1 (2012). 14 a.Cl Biol. Cell Nat. ur Biol. Curr. 21) h d8 oprgo facilitates region loop Ndc80 The (2011). 561-563. , 34 Cell 21) N1Sc0 erisP1to PP1 recruits KNL1/Spc105 (2011). 1070-1077. , .Cl Biol. Cell J. 21) oeua rhtcueand architecture Molecular (2010). Cell 127 20) ieohr attachments Kinetochore (2008). .Cl Biol. Cell J. 20) oeo e1i spindle in Hec1 of Role (2002). 20) h d8 kinetochore Ndc80 The (2009). 21 1179-1191. , 43 6 70 942-947. , 1135-1141. , 21) pnl checkpoint Spindle (2011). Chromosoma 439-465. , 115-125. , 20) Intrakinetochore (2009). 21) CENP-T-W-S-X (2012). 190 elSci. Cell J 73-87. , 190 Science Chromosoma 823-834. , 116 MOJ. EMBO e.Cell Dev. 21) The (2010). ur Biol. Curr. 297 385-402. , 123 a.Cell Nat. Cell (2010). (2009). 2267- , .Cell J. 825- , 148 120 28 20 , , , , e,R . lBsa,J n arsn .C. S. Harrison, and and G. J. Al-Bassam, Barnes, R., D., R. Drubin, Wei, S., Westermann, C., Ciferri, S., Long, W., H. Wang, ag . u . ig . o,Z,Yn,Z,Sa,A . eg . Cleveland, M., Teng, W., A. Shaw, Z., Yang, Z., Dou, X., Ding, G., X., J. Hu, DeLuca, H., E., Wang, W. Gall, P., A. Joglekar, L., H. Pierce, P., R. O’Quinn, X., Wan, Labbe C., Bernis, S., Prieto, S., Vigneron, o,L . ausi .K n hn .K. G. Chan, and K. J. Famulski, J., L. Vos, M. D. Glover, and R. M. Przewloka, Z., Venkei, hped .A,Maos .C,Sca,A . acse,T . o,J,Buttrick, J., Zou, C., T. Lancaster, M., A. Sochaj, C., J. Meadows, A., L. Shepperd, ceat,E,D noi . lsi,G . ervc . ei,T,Ngls .and E. Nogales, T., Melis, A., Petrovic, M., G. Alushin, A., Antoni, De Wilson- E., Screpanti, M., N. Dashkevich, A., Boeszoermenyi, H., Arthanari, C., J. Schmidt, am,D,Cadaeaa,S,Sni,L . ed,K . a,X,Cas,D A., D. Chasse, X., Wan, T., K. Reidy, J., L. Sundin, S., Chandrasekaran, D., Varma, mri,N . etu,D . in .F,Vlmr .S,Gnn . suy .L. C. Asbury, T., Gonen, S., B. Vollmar, F., J. Tien, R., D. Gestaut, T., N. Umbreit, T. P. Stukenberg, and A. S. Miller, T. G., J. P. Tooley, Stukenberg, and J. Tooley, hn,G,Kltu,C . u .W,Ka asn .J,Snltn .R,Olsen, R., M. Singleton, J., M. Hansen, Kaas W., X. Hu, D., Y. C. Watanabe, Kelstrup, G., and Zhang, Y. Tanno, H., C. Yang, Y., Yamagishi, hi,M,Saik,M,Jnuia . azosiRgc,M,Sontheimer, M., Paszkowski-Rogacz, M., Junqueira, M., Slabicki, M., Theis, isnKblk .M,Cesmn .M,Ysik,C,Dsi .adMilligan, and A. Desai, C., Yoshioka, M., I. Cheeseman, M., E. Wilson-Kubalek, T. Fukagawa, A., M. Lampson, 3rd, R., J. Yates, Yates, D., M., Liu, M., E. Vleugel, P., Wilson-Kubalek, J. Welburn, B., C. Backer, L., E. Grishchuk, P., J. Welburn, aeci .adFkgw,T. Fukagawa, and K. G. J. Takeuchi, Deluca, and J. G. Guimaraes, J., L. Sundin, e,R,No . u .adLe .H. W. Lee, and G. Wu, B., Ngo, R., Wei, tr,D . afr,R,L,Z,Smsn .E,Co,K . e,T .and J. T. Yen, H., K. Choo, E., A. Simpson, Z., Li, R., Saffery, A., D. Starr, complex. E. Nogales, fZseWie1 okntcoe n sesnilfrmttccekon signaling. checkpoint mitotic for essential is and al. Chem. kinetochores Biol. to et J. 10 al. F. et White L. B. Zeste Niu, of L., McEwen, M. Goldberg, J., W., T. D. Yen, site. attachment T., microtubule kinetochore S. human the Liu, of architecture W., C. Carroll, ue ieohr:ietfcto ftekntcoelclzto oanadthe and domain localization kinetochore the of domain. hZw10-interaction identification kinetochore: outer whom? controls who proteins: checkpoint Cell Biol. spindle of a localization and Kinetochore movement chromosome anaphase for checkpoint. essential assembly unit spindle functional robust single a as acts erimn fBb n u3t p7KL yMh iaemitistespindle the maintains kinase Mph1 by Spc7/KNL1 to B. Bub3 J. checkpoint. Millar, and and Bub1 G. of K. recruitment Hardwick, J., Rappsilber, J., G. ne n ue kinetochore. outer and inner A. Musacchio, Bathe, protofilaments. A., curved R. to Milligan, binds M., and Oberer, al. microtubules M., Markus, et N., M. Monnier, M., E. Kubalek, h ua d1rpiainlcnigpoenb h opdmi fHc srequired is Hec1 of domain loop attachment. G. the J. kinetochore-microtubule by Cook, protein stable and licensing for D. replication E. Cdt1 Salmon, human G., the J. DeLuca, R., K. Nevis, n ai,T N. dynamics. microtubule T. Davis, and chromosome to depolymerization microtubule couple to movement. point attachment tripartite h k ope oetbihedo irtbl tahett kinetochores. to attachment microtubule end-on establish Sci. to complex Ska J. the Nilsson, and V. J. components. SAC recruit to Biol. KNL1/Spc7 Cell protein kinetochore the phosphorylates ieohr’ aymovements. many kinetochore’s required al. complex et Ska division. I. the cell of Poser, mammalian component K., a for Kruusmaa, as T., C13orf3 Glatter, identifies K., profiling Comparative A. Heninger, R., Kittler, J., lattice. A. R. interface. kinetochore-microtubule the regulate differentially M. I. Cheeseman, and M. motility. I. depolymerization-coupled Cheeseman, microtubule and facilitates 3rd R., J. kinetochores. ope rti,HC,b e2kns ouae hoooeainetand alignment chromosome modulates checkpoint. kinase assembly spindle Nek2 the by of signaling HEC1, protein, complex rtisNf n e1mk itntcnrbtost kinetochore-microtubule to contributions distinct make mitosis. Hec1 in attachment and Nuf2 proteins HZW10. with interacts L. M. Goldberg, otc on o ieohr-irtbl attachment. kinetochore-microtubule for point contact 125 20) retto n tutr fteNc0cmlxo h microtubule the on complex Ndc80 the of structure and Orientation (2008). .Cl Biol. Cell J. 3243-3253. , .Ml Biol. Mol. J. 15 14 o.Bo.Cell Biol. Mol. 21) h ieohr-on k1cmlxtak depolymerizing tracks complex ska1 kinetochore-bound The (2012). ur Biol. Curr. 4584-4596. , 746-752. , 20) rhtcueadfeiiiyo h es d8 kinetochore Ndc80 yeast the of flexibility and Architecture (2008). x.Cl Res. Cell Exp. 279 21) ietbnigo epCt h i1 ope on the joins complex Mis12 the to Cenp-C of binding Direct (2011). 54590-54598. , 20) Zit1 oe ua ieohr opnn that component kinetochore human novel a HZwint-1, (2000). 182 21) h d8 ieohr ope ietymodulates directly complex kinetochore Ndc80 The (2012). 21) h d8 nenllo srqie o erimn of recruitment for required is loop internal Ndc80 The (2012). o.Bo.Cell Biol. Mol. 383 rc al cd c.USA Sci. Acad. Natl. Proc. .Cl Sci. Cell J. 22 1055-1061. , 21) uoaBpopoyae ptal itnttresto targets distinct spatially phosphorylates B Aurora (2010). 891-899. , 894-903. , 22 ice.J. Biochem. ur Biol. Curr. 318 MOJ. EMBO 1217-1226. , 1367-1374. , hoooeRes. Chromosome 113 21) oeua rhtcueo vertebrate of architecture Molecular (2012). 21) h d8 ope:itgaigthe integrating complex: Ndc80 The (2011). 20) h ua ieohr k1complex Ska1 kinetochore human The (2009). Genetics 22 1939-1950. , 20) ua wn- pcfe localization specifies Zwint-1 Human (2004). 28 436 21 ,J . ato .adLra T. Lorca, and A. Castro, C., J. ´, 759-768. , 1453-1465. , 391-398. , 157-168. , 21) Zit1bigsteinrand inner the bridges hZwint-1 (2011). 21) hshrlto fteNdc80 the of Phosphorylation (2011). 20) h d8/E1cmlxi a is complex Ndc80/HEC1 The (2007). 187 o.Bo.Cell Biol. Mol. a.Cl Biol. Cell Nat. 21) rspiaMs2complex Mis12 Drosophila (2011). 21) h d8 ope ssa uses complex Ndc80 The (2011). 131-140. , e.Cell Dev. 109 19 a.Src.Ml Biol. Mol. Struct. Nat. 21) h D8 complex NDC80 The (2011). 377-391. , 16113-16118. , 21) Phosphodependent (2012). e.Cell Dev. o.Cell Mol. 23 21) erimn of Recruitment (2012). 22 968-980. , 14 21) MPS1/Mph1 (2012). 3584-3594. , 593-603. , Cell 20) Protein (2009). 16 38 137 374-385. , 383-392. , 672-684. , 14 54-59. , (2004). (2009). .Cell J. Mol. Nat.