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Nucleic Acids Research Executive editors R.T.Walker, Birmingham, UK M.J.Gait, Cambridge, UK R.B.Hallick, Tucson, AZ, USA R.J.Roberts, Beverly, MA, USA H.J.Gross, Wulrzburg, Germany S.Linn, Berkeley, CA, USA K.Calame, New York, NY, USA R.I.Gumport, Urbana, IL, USA R.T.Simpson, University Park, PA, USA I.C.Eperon, Leicester, UK Editorial board A.Bairoch, Geneva, Switzerland J.E.Hearst, Berkeley, CA, USA M.G.Parker, London, UK M.Beato, Marburg, Germany C.Helene, Paris, France R.K.Patient, London, UK M.Belfort, Albany, NY, USA A.J.Jeffreys, Leicester, UK M.Paule, Fort Collins, CO, USA M.Busslinger, Vienna, Austria S.-H.Kim, Berkeley, CA, USA A.M.Pyle, New York, NY, USA H.Cedar, Jerusalem, Israel A.R.Krainer, CSHL, NY, USA J.M.Rosen, Houston, TX, USA R.Dalgleish, Leicester, UK R.Krumlauf, London, UK H.Ruterjans, Frankfurt, Germany M.L.DePamphilis, Nutley, NJ, USA A.Lamond, Dundee, UK C.W.Schmid, Davis, CA, USA W.Dynan, Boulder, CO, USA D.S.Latchman, London, UK P.M.Sharp, Nottingham, UK F.Eckstein, Gdttingen, Germany C.J.Leaver, Oxford, UK L.Simpson, Los Angeles, CA, USA J.D.Engel, Evanston, IL, USA D.M.J.Lilley, Dundee, UK S.T.Smale, Los Angeles, CA, USA P.T.Englund, Baltimore, MD, USA J.T.Lis, Ithaca, NY, USA G.Stormo, Boulder, CO, USA D.J.Finnegan, Edinburgh, UK R.Luhrman, Marburg, Germany R.H.Symons, Adelaide, Australia M.Gellert, Bethesda, MD, USA N.C.Martin, Louisville, KY, USA K.Taira, Tsukuba, Japan R.Giege, Strasbourg, France M.McClelland, La Jolla, CA, USA I.Tinoco, Jr, Berkeley, CA, USA L.A.Grivell, Amsterdam, The Netherlands W.R.McClure, Pittsburgh, PA, USA B.Van Ness, Minneapolis, MN, USA W.Gruissem, Berkeley, CA, USA M.Muramatsu, Saitama, Japan A.M.Weiner, New Haven, CT, USA W.Guschlbauer, Gif-sur-Yvette, France E.Ohtsuka, Sapporo, Japan S.C.West, South Mimms, Herts, UK S.E.Halford, Bristol, UK H.Okayama, Tok;yo, Japan J.A.Wise, Cleveland, OH, USA D.Hawley, Eugene, OR, USA M.V.Olson, Seattle, WA, USA G.Zon, Foster City, CA, USA Editorial and Production Joy Walker, UK Editorial Office Sarah Brennan, Production Editor Carol Cook, US Editorial Office Jaqueline Grainger, Production Assistant Robert Blundell, Production Assistant OXFORD UNIVERSITY PRESS Subscriptions Nucleic Acids Research is published semi-monthly (24 issues) with an Annual K Oxford University Press 1995. 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To advertise in Nucleic Acids Research contact Oxford University Press (US office) in the Americas or Oxford University Press (UK office) in the Rest of the World (see addresses above). Printed by Information Press Ltd, Oxford, UK on permanent Paper. Cover: The dynamic equilibrium in the control element of the S15 messenger RNA between two hairpins (top left) and a pseudoknot (bottom right). The helix in yellow is present in both structures. The pseudoknot invofves base pairing between the loop in green and the strand in red of the other hairpin. See paper by C. Philippe et al., Nucleic Acids Res. 23, 18-28. Drawing made on a Silicon Graphics EXTREME2 with the program DRAWNA [C. Massive et al., J. Mol. Graph. 12, 201 (1994)]. Authors submitting an article containing a photograph which may be suitable for use on the cover of Nucleic Acids Research are encouraged to contact an executive editor. Packed into the December issue of HMG . ARTICLES Mutation analysis ofthe TSC2 gene in an African-American Identification ofcentromeric antigens in dicentric Robertsonian family. A Kumar, R S Kandt, C Wolpert, A D Roses, M A Pericak- translocations: CENP-C AND CENP-E are necessary components Vance and J R Gilbert P.2295 of functional centromeres B A Sullivan and S Schwartz P 2189 T->A transversion 11 bp from a splice acceptor site in the human Population survey ofthe human FMR1 CGG repeat substructure gene for steroidogenic acute regulatory protein causes congenital suggests biased polarity for the loss ofAGG lipoid adrenal hyperplasia. M-K Tee, D Lin, T Sugawara, J A Holt, interruptions. E E Eichler, H A Hammond, j N Macpherson, Y Guiguen, B Buckingham, J F Strauss III andW L Miller P.2299 P AWard and D L Nelson P 2199 RBM3, a novel human gene in Xpl 1.23 with a putative RNA- Highly conserved 3' UTR and expression pattern of FXR1 points binding domain. J M j Derry, J A Kerns and U Francke P.2307 to a divergent gene regulation of FXR1 and FMR1. J F Coy, Z Sedlacek, D Bachner, H Hameister, S joos, P Lichter, H Delius Breakpoint characterization ofthe ret/PTC oncogene in human and A Poustka P2209 papillary thyroid carcinoma. P A Smanik, T L Furminger, E L Mazzaferri and S M Jhiang P.2313 Oncogenic conversion of a novel orphan nudear receptor by chromosome translocation. Y Labelle,j Zucman, G Stenman, Analysis ofthe OA1 gene reveals mutations in only one-third of L-G Kindblom, J Knight, C Turc-Carel, B Dockhorn- patients with X-linked ocular albinism. M V Schiaffino, M T Bassi, Dworniczak, N Mandahl, C Desmuze, M Peter, A Aurias, 0 L Galli, A Renieri, M Bruttini, F De Nigris, A A B Bergen, S J Delattre and G Thomas P2219 Charles, J RWYates, A Meindl, R A Lewis, R A King and A Ballabio P.2319 REPORTS Analysis ofthe CMTIA-REP repeat: mapping crossover breakpoints Non-disjunction in human sperm: evidence for an effect of in CMTIA and HNPP. H Kiyosawa, M W Lensch and P F Chance increasing paternal age. D K Griffin, M A Abruzzo, E A Millie, P2327 L A Sheean, E Feingold, S L Sherman and T J Hassold P.2227 Characterization ofthe large deletion in the GALC gene found Stability ofthe Huntington disease (CAG)n repeat in a late- in patients with Krabbe disease. P Luzi, M A Rafi and D A Wenger onset form occurring on the Island ofCrete. M Tzagoumissakis, P.2335 C 0 Fesdjian, P Shashidharan and A Plaitakis P2239 A gene (SRPX) encoding a sushi-repeat-containing protein is Lowe Syndrome, a deficiency of a phosphatidyl-inositol 4,5- deleted in patients with X-linked retinitis pigmentosa. A Meindl, bisphophate 5-phosphatase in the Golgi apparatus. S F Suchy, M R S Carvalho, K Herrmann, B Lorenz, H Achatz, B Lorenz, I M Olivos-Glander and R L Nussbaum P2245 E Apfelstedt-Sylla, B Wittwer, M Ross and T Meitinger P2339 Homologous unequal cross-over involving a 2.8 kb direct repeat as a mechanism for the generation ofallelic variants ofthe human Find out more - On the Internet ! cytochrome P450 CYP2D6 gene. V M Steen, A Molven, N K Aarskog and A-K Gulbrandsen P.225 1 The above is just a partial list of the December issue contents. Ifyou have access to the internet, then you can Distinct transcription start sites generate two forms of BRCA1 join for FREE, the Human Molecular Genetics internet mRNA. C-F Xu, M A Brown, J A Chambers, B Griffiths, H mailing list and receive regular information on the entire I Nicolai and E Solomon P2259 contents ofeach issue, delivered direct to your mailbox | Mouse Brcal: sequence and identification of localization, analysis some 2 to 3 weeks before publication.
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  • 6.Start.Stop.07.Ppt [Read-Only]

    6.Start.Stop.07.Ppt [Read-Only]

    Accessory factors summary 1. DNA polymerase can’t replicate a genome. Solution ATP? No single stranded template Helicase + The ss template is unstable SSB (RPA (euks)) - No primer Primase (+) No 3’-->5’ polymerase Replication fork Too slow and distributive SSB and sliding clamp - Sliding clamp can’t get on Clamp loader (γ/RFC) + Lagging strand contains RNA Pol I 5’-->3’ exo, RNAseH - Lagging strand is nicked DNA ligase + Helicase introduces + supercoils Topoisomerase II + and products tangled 2. DNA replication is fast and processive DNA polymerase holoenzyme 1 Maturation of Okazaki fragments Topoisomerases control chromosome topology Catenanes/knots Topos Relaxed/disentangled •Major therapeutic target - chemotherapeutics/antibacterials •Type II topos transport one DNA through another 2 Starting and stopping summary 1. DNA replication is controlled at the initiation step. 2. DNA replication starts at specific sites in E. coli and yeast. 3. In E. coli, DnaA recognizes OriC and promotes loading of the DnaB helicase by DnaC (helicase loader) 4. DnaA and DnaC reactions are coupled to ATP hydrolysis. 5. Bacterial chromosomes are circular, and termination occurs opposite OriC. 6. In E. coli, the helicase inhibitor protein, tus, binds 7 ter DNA sites to trap the replisome at the end. 7. Eukaryotic chromosomes are linear, and the chromosome ends cannot be replicated by the replisome. 8. Telomerase extends the leading strand at the end. 9. Telomerase is a ribonucleoprotein (RNP) with RNA (template) and reverse-transcriptase subunits. Isolating DNA sequences that mediate initiation 3 Different origin sequences in different organisms E. Coli (bacteria) OriC Yeast ARS (Autonomously Replicating Sequences) Metazoans ???? Initiation in prokaryotes and eukaryotes Bacteria Eukaryotes ORC + other proteins load MCM hexameric helicases MCM (helicase) + RPA (ssbp) Primase + DNA pol α PCNA:pol δ + RFC MCM (helicase) + RPA (ssbp) PCNA:pol δ + RFC (clamp loader) Primase + DNA pol α PCNA:pol δ + DNA ligase 4 Crystal structure of DnaA:ATP revealed mechanism of origin assembly 1.