Molecular Determinants of the Ska-Ndc80 Interaction and Their
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PDW CV March 2014
Curriculum Vitae Dr. ir. Peter De Wulf Contact information European Institute of Oncology Department of Experimental Oncology Via Adamello 16 20139 Milan, Italy E-mail: [email protected] Tel: (++39) 0294375036 Fax: (++39) 0294375990 Position 08/2005 - present Principal Investigator Director Kinetochore and Chromosome Segregation Research Unit Department of Experimental Oncology European Institute of Oncology Milan, Italy Education and training 11/1999 - 06/2005 Post-Doctoral Research in Yeast Kinetochore Biology Department of Biology Massachusetts Institute of Technology 77 Massachusetts Avenue 02139 Cambridge (MA), USA Mentor: Prof. Dr. Peter K. Sorger (now at Harvard Medical School, Department of Systems Biology) 07/1996 - 10/1999 Post-Doctoral Research in Bacterial Two-Component Signal Transduction Department of Microbiology and Molecular Genetics Harvard Medical School 210 Longwood Avenue 02115 Boston (MA), USA Mentor: Prof. Dr. Edmund C.C. Lin (deceased) 04-20/07/1999 Course in Protein Purification and Characterization Cold Spring Harbor Laboratory. Cold Spring Harbor (NY), USA Instructors: Dr. Richard Burgess, Dr. Albert Courey, Dr. Sue-Hwa Lin, Dr. Sheenah Mische 06-20/06/1997 Course in Advanced Bacterial Genetics Cold Spring Harbor Laboratory. Cold Spring Harbor (NY), USA Instructors: Dr. Bonnie Bassler, Dr. Colin Manoil, Dr. James Slauch 06/1995 - 06/1996 Training in Yeast Cell Biology Department of Applied Biochemistry University of Milan via Celoria 26 20133 Milan, Italy Mentor: Prof. Dr. Lilia Alberghina (now at the University of Milan-Bicocca, Department of Biotechnology and Biosciences) 1 01/1992-05/1995 Ph.D. in Industrial Microbiology and Biocatalysis Department of Biochemical and Microbial Technology School of Bioengineering University of Ghent Coupure Links 653 B-9000 Ghent, Belgium Mentor: Prof. -
Aurora B-Dependent Ndc80 Degradation Regulates
bioRxiv preprint doi: https://doi.org/10.1101/836668; this version posted November 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Aurora B-dependent Ndc80 Degradation Regulates Kinetochore Composition in 2 Meiosis 3 4 5 Running title: Aurora B Regulates Ndc80 Proteolysis in Meiosis 6 7 Keywords: meiosis, kinetochore, Aurora B, Ndc80, chromosome, proteolysis, APC 8 9 10 Jingxun Chen1, Andrew Liao1, Emily N Powers1, Hanna Liao1, Lori A Kohlstaedt2, Rena 11 Evans3, Ryan M Holly1, Jenny Kim Kim4, Marko Jovanovic4 and Elçin Ünal1, § 12 13 1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 14 94720, United States 15 2 UC Berkeley QB3 Proteomics Facility, University of California, Berkeley, CA 94720, 16 United States 17 3 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States 18 4 Department of Biology, Columbia University, New York City, NY 10027, United States 19 20 § Correspondence: [email protected] 21 22 23 24 25 26 1 bioRxiv preprint doi: https://doi.org/10.1101/836668; this version posted November 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 27 ABSTRACT 28 29 The kinetochore complex is a conserved machinery that connects chromosomes to 30 spindle microtubules. -
The MIS12 Complex Is a Protein Interaction Hub for Outer Kinetochore Assembly
JCB: Article The MIS12 complex is a protein interaction hub for outer kinetochore assembly Arsen Petrovic,1 Sebastiano Pasqualato,1 Prakash Dube,3 Veronica Krenn,1 Stefano Santaguida,1 Davide Cittaro,4 Silvia Monzani,1 Lucia Massimiliano,1 Jenny Keller,1 Aldo Tarricone,1 Alessio Maiolica,1 Holger Stark,3 and Andrea Musacchio1,2 1Department of Experimental Oncology, European Institute of Oncology (IEO) and 2Research Unit of the Italian Institute of Technology, Italian Foundation for Cancer Research Institute of Molecular Oncology–IEO Campus, I-20139 Milan, Italy 33D Electron Cryomicroscopy Group, Max Planck Institute for Biophysical Chemistry, and Göttingen Center for Microbiology, University of Göttingen, 37077 Göttingen, Germany 4Consortium for Genomic Technologies, I-20139 Milan, Italy inetochores are nucleoprotein assemblies responsi axis of 22 nm. Through biochemical analysis, cross- ble for the attachment of chromosomes to spindle linking–based methods, and negative-stain electron mi K microtubules during mitosis. The KMN network, croscopy, we investigated the reciprocal organization of a crucial constituent of the outer kinetochore, creates an the subunits of the MIS12 complex and their contacts with interface that connects microtubules to centromeric chro the rest of the KMN network. A highlight of our findings matin. The NDC80, MIS12, and KNL1 complexes form the is the identification of the NSL1 subunit as a scaffold core of the KMN network. We recently reported the struc supporting interactions of the MIS12 complex with the tural organization of the human NDC80 complex. In this NDC80 and KNL1 complexes. Our analysis has important study, we extend our analysis to the human MIS12 com implications for understanding kinetochore organization in plex and show that it has an elongated structure with a long different organisms. -
Congenital Microcephaly
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Sussex Research Online American Journal of Medical Genetics Part C (Seminars in Medical Genetics) ARTICLE Congenital Microcephaly DIANA ALCANTARA AND MARK O'DRISCOLL* The underlying etiologies of genetic congenital microcephaly are complex and multifactorial. Recently, with the exponential growth in the identification and characterization of novel genetic causes of congenital microcephaly, there has been a consolidation and emergence of certain themes concerning underlying pathomechanisms. These include abnormal mitotic microtubule spindle structure, numerical and structural abnormalities of the centrosome, altered cilia function, impaired DNA repair, DNA Damage Response signaling and DNA replication, along with attenuated cell cycle checkpoint proficiency. Many of these processes are highly interconnected. Interestingly, a defect in a gene whose encoded protein has a canonical function in one of these processes can often have multiple impacts at the cellular level involving several of these pathways. Here, we overview the key pathomechanistic themes underlying profound congenital microcephaly, and emphasize their interconnected nature. © 2014 Wiley Periodicals, Inc. KEY WORDS: cell division; mitosis; DNA replication; cilia How to cite this article: Alcantara D, O'Driscoll M. 2014. Congenital microcephaly. Am J Med Genet Part C Semin Med Genet 9999:1–16. INTRODUCTION mid‐gestation although glial cell division formation of the various cortical layers. and consequent brain volume enlarge- Furthermore, differentiating and devel- Congenital microcephaly, an occipital‐ ment does continue after birth [Spalding oping neurons must migrate to their frontal circumference of equal to or less et al., 2005]. Impaired neurogenesis is defined locations to construct the com- than 2–3 standard deviations below the therefore most obviously reflected clini- plex architecture and laminar layered age‐related population mean, denotes cally as congenital microcephaly. -
1 AGING Supplementary Table 2
SUPPLEMENTARY TABLES Supplementary Table 1. Details of the eight domain chains of KIAA0101. Serial IDENTITY MAX IN COMP- INTERFACE ID POSITION RESOLUTION EXPERIMENT TYPE number START STOP SCORE IDENTITY LEX WITH CAVITY A 4D2G_D 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ B 4D2G_E 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ C 6EHT_D 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ D 6EHT_E 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ E 6GWS_D 41-72 41 72 100 100 3.2Å PCNA X-RAY DIFFRACTION √ F 6GWS_E 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ G 6GWS_F 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ H 6IIW_B 2-11 2 11 100 100 1.699Å UHRF1 X-RAY DIFFRACTION √ www.aging-us.com 1 AGING Supplementary Table 2. Significantly enriched gene ontology (GO) annotations (cellular components) of KIAA0101 in lung adenocarcinoma (LinkedOmics). Leading Description FDR Leading Edge Gene EdgeNum RAD51, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, CENPW, HJURP, NDC80, CDCA5, NCAPH, BUB1, ZWILCH, CENPK, KIF2C, AURKA, CENPN, TOP2A, CENPM, PLK1, ERCC6L, CDT1, CHEK1, SPAG5, CENPH, condensed 66 0 SPC24, NUP37, BLM, CENPE, BUB3, CDK2, FANCD2, CENPO, CENPF, BRCA1, DSN1, chromosome MKI67, NCAPG2, H2AFX, HMGB2, SUV39H1, CBX3, TUBG1, KNTC1, PPP1CC, SMC2, BANF1, NCAPD2, SKA2, NUP107, BRCA2, NUP85, ITGB3BP, SYCE2, TOPBP1, DMC1, SMC4, INCENP. RAD51, OIP5, CDK1, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, ESCO2, CENPW, HJURP, TTK, NDC80, CDCA5, BUB1, ZWILCH, CENPK, KIF2C, AURKA, DSCC1, CENPN, CDCA8, CENPM, PLK1, MCM6, ERCC6L, CDT1, HELLS, CHEK1, SPAG5, CENPH, PCNA, SPC24, CENPI, NUP37, FEN1, chromosomal 94 0 CENPL, BLM, KIF18A, CENPE, MCM4, BUB3, SUV39H2, MCM2, CDK2, PIF1, DNA2, region CENPO, CENPF, CHEK2, DSN1, H2AFX, MCM7, SUV39H1, MTBP, CBX3, RECQL4, KNTC1, PPP1CC, CENPP, CENPQ, PTGES3, NCAPD2, DYNLL1, SKA2, HAT1, NUP107, MCM5, MCM3, MSH2, BRCA2, NUP85, SSB, ITGB3BP, DMC1, INCENP, THOC3, XPO1, APEX1, XRCC5, KIF22, DCLRE1A, SEH1L, XRCC3, NSMCE2, RAD21. -
Real-Time Dynamics of Plasmodium NDC80 Reveals Unusual Modes of Chromosome Segregation During Parasite Proliferation Mohammad Zeeshan1,*, Rajan Pandey1,*, David J
© 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2021) 134, jcs245753. doi:10.1242/jcs.245753 RESEARCH ARTICLE SPECIAL ISSUE: CELL BIOLOGY OF HOST–PATHOGEN INTERACTIONS Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation Mohammad Zeeshan1,*, Rajan Pandey1,*, David J. P. Ferguson2,3, Eelco C. Tromer4, Robert Markus1, Steven Abel5, Declan Brady1, Emilie Daniel1, Rebecca Limenitakis6, Andrew R. Bottrill7, Karine G. Le Roch5, Anthony A. Holder8, Ross F. Waller4, David S. Guttery9 and Rita Tewari1,‡ ABSTRACT eukaryotic organisms to proliferate, propagate and survive. During Eukaryotic cell proliferation requires chromosome replication and these processes, microtubular spindles form to facilitate an equal precise segregation to ensure daughter cells have identical genomic segregation of duplicated chromosomes to the spindle poles. copies. Species of the genus Plasmodium, the causative agents of Chromosome attachment to spindle microtubules (MTs) is malaria, display remarkable aspects of nuclear division throughout their mediated by kinetochores, which are large multiprotein complexes life cycle to meet some peculiar and unique challenges to DNA assembled on centromeres located at the constriction point of sister replication and chromosome segregation. The parasite undergoes chromatids (Cheeseman, 2014; McKinley and Cheeseman, 2016; atypical endomitosis and endoreduplication with an intact nuclear Musacchio and Desai, 2017; Vader and Musacchio, 2017). Each membrane and intranuclear mitotic spindle. To understand these diverse sister chromatid has its own kinetochore, oriented to facilitate modes of Plasmodium cell division, we have studied the behaviour movement to opposite poles of the spindle apparatus. During and composition of the outer kinetochore NDC80 complex, a key part of anaphase, the spindle elongates and the sister chromatids separate, the mitotic apparatus that attaches the centromere of chromosomes to resulting in segregation of the two genomes during telophase. -
Kinetochores, Microtubules, and Spindle Assembly Checkpoint
Review Joined at the hip: kinetochores, microtubules, and spindle assembly checkpoint signaling 1 1,2,3 Carlos Sacristan and Geert J.P.L. Kops 1 Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands 2 Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands 3 Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands Error-free chromosome segregation relies on stable and cell division. The messenger is the SAC (also known as connections between kinetochores and spindle microtu- the mitotic checkpoint) (Figure 1). bules. The spindle assembly checkpoint (SAC) monitors The transition to anaphase is triggered by the E3 ubiqui- such connections and relays their absence to the cell tin ligase APC/C, which tags inhibitors of mitotic exit cycle machinery to delay cell division. The molecular (CYCLIN B) and of sister chromatid disjunction (SECURIN) network at kinetochores that is responsible for microtu- for proteasomal degradation [2]. The SAC has a one-track bule binding is integrated with the core components mind, inhibiting APC/C as long as incorrectly attached of the SAC signaling system. Molecular-mechanistic chromosomes persist. It goes about this in the most straight- understanding of how the SAC is coupled to the kineto- forward way possible: it assembles a direct and diffusible chore–microtubule interface has advanced significantly inhibitor of APC/C at kinetochores that are not connected in recent years. The latest insights not only provide a to spindle microtubules. This inhibitor is named the striking view of the dynamics and regulation of SAC mitotic checkpoint complex (MCC) (Figure 1). -
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HP-1α mouse Monoclonal Antibody(2G2) Catalog No : YM3794 Reactivity : Human,Mouse,Rat Applications : WB,IHC-p,IF(paraffin section) Gene Name : CBX5 HP1A Protein Name : Chromobox protein homolog 5 (Antigen p25) (Heterochromatin protein 1 homolog alpha) (HP1 alpha) Human Gene Id : 23468 Human Swiss Prot P45973 No : Mouse Swiss Prot Q61686 No : Immunogen : Recombinant Protein of HP-1α Specificity : The antibody detects endogenous HP-1α protein Formulation : Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide. Source : Mouse Dilution : WB 1:500-2000,IHC-p 1:50-300 Purification : The antibody was affinity-purified from mouse antiserum by affinity- chromatography using epitope-specific immunogen. Concentration : 1 mg/ml Storage Stability : -20°C/1 year Observed Band : 22 Background : chromobox 5(CBX5) Homo sapiens This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family. The 1 / 2 protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The encoded product is involved in the formation of functional kinetochore through interaction with essential kinetochore proteins. The gene has a pseudogene located on chromosome 3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008], Function : function:Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. -
Molecular Genetics of Microcephaly Primary Hereditary: an Overview
brain sciences Review Molecular Genetics of Microcephaly Primary Hereditary: An Overview Nikistratos Siskos † , Electra Stylianopoulou †, Georgios Skavdis and Maria E. Grigoriou * Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; [email protected] (N.S.); [email protected] (E.S.); [email protected] (G.S.) * Correspondence: [email protected] † Equal contribution. Abstract: MicroCephaly Primary Hereditary (MCPH) is a rare congenital neurodevelopmental disorder characterized by a significant reduction of the occipitofrontal head circumference and mild to moderate mental disability. Patients have small brains, though with overall normal architecture; therefore, studying MCPH can reveal not only the pathological mechanisms leading to this condition, but also the mechanisms operating during normal development. MCPH is genetically heterogeneous, with 27 genes listed so far in the Online Mendelian Inheritance in Man (OMIM) database. In this review, we discuss the role of MCPH proteins and delineate the molecular mechanisms and common pathways in which they participate. Keywords: microcephaly; MCPH; MCPH1–MCPH27; molecular genetics; cell cycle 1. Introduction Citation: Siskos, N.; Stylianopoulou, Microcephaly, from the Greek word µικρoκεϕαλi´α (mikrokephalia), meaning small E.; Skavdis, G.; Grigoriou, M.E. head, is a term used to describe a cranium with reduction of the occipitofrontal head circum- Molecular Genetics of Microcephaly ference equal, or more that teo standard deviations -
Discovery of Novel Putative Tumor Suppressors from CRISPR Screens Reveals Rewired 2 Lipid Metabolism in AML Cells 3 4 W
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.08.332023; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Discovery of novel putative tumor suppressors from CRISPR screens reveals rewired 2 lipid metabolism in AML cells 3 4 W. Frank Lenoir1,2, Micaela Morgado2, Peter C DeWeirdt3, Megan McLaughlin1,2, Audrey L 5 Griffith3, Annabel K Sangree3, Marissa N Feeley3, Nazanin Esmaeili Anvar1,2, Eiru Kim2, Lori L 6 Bertolet2, Medina Colic1,2, Merve Dede1,2, John G Doench3, Traver Hart2,4,* 7 8 9 1 - The University of Texas MD Anderson Cancer Center UTHealth Graduate School of 10 Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX 11 12 2 - Department of Bioinformatics and Computational Biology, The University of Texas MD 13 Anderson Cancer Center, Houston, TX, USA 14 15 3 - Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA 16 17 4 - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 18 Houston, TX, USA 19 20 21 22 23 * - Corresponding author: [email protected] 24 25 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.08.332023; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Bub1 Positions Mad1 Close to KNL1 MELT Repeats to Promote Checkpoint Signalling
ARTICLE Received 14 Dec 2016 | Accepted 3 May 2017 | Published 12 June 2017 DOI: 10.1038/ncomms15822 OPEN Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling Gang Zhang1, Thomas Kruse1, Blanca Lo´pez-Me´ndez1, Kathrine Beck Sylvestersen1, Dimitriya H. Garvanska1, Simone Schopper1, Michael Lund Nielsen1 & Jakob Nilsson1 Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct interactions. Here we show that conserved domain 1 (CD1) in human Bub1 binds directly to Mad1 and a phosphorylation site exists in CD1 that stimulates Mad1 binding and SAC signalling. Importantly, fusion of minimal kinetochore-targeting Bub1 fragments to Mad1 bypasses the need for CD1, revealing that the main function of Bub1 is to position Mad1 close to KNL1 MELTrepeats. Furthermore, we identify residues in Mad1 that are critical for Mad1 functionality, but not Bub1 binding, arguing for a direct role of Mad1 in the checkpoint. This work dissects functionally relevant molecular interactions required for spindle assembly checkpoint signalling at kinetochores in human cells. 1 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. Correspondence and requests for materials should be addressed to G.Z. -
Molecular Features of Triple Negative Breast Cancer Cells by Genome-Wide Gene Expression Profiling Analysis
478 INTERNATIONAL JOURNAL OF ONCOLOGY 42: 478-506, 2013 Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis MASATO KOMATSU1,2*, TETSURO YOSHIMARU1*, TAISUKE MATSUO1, KAZUMA KIYOTANI1, YASUO MIYOSHI3, TOSHIHITO TANAHASHI4, KAZUHITO ROKUTAN4, RUI YAMAGUCHI5, AYUMU SAITO6, SEIYA IMOTO6, SATORU MIYANO6, YUSUKE NAKAMURA7, MITSUNORI SASA8, MITSUO SHIMADA2 and TOYOMASA KATAGIRI1 1Division of Genome Medicine, Institute for Genome Research, The University of Tokushima; 2Department of Digestive and Transplantation Surgery, The University of Tokushima Graduate School; 3Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Hyogo 663-8501; 4Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503; Laboratories of 5Sequence Analysis, 6DNA Information Analysis and 7Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639; 8Tokushima Breast Care Clinic, Tokushima 770-0052, Japan Received September 22, 2012; Accepted November 6, 2012 DOI: 10.3892/ijo.2012.1744 Abstract. Triple negative breast cancer (TNBC) has a poor carcinogenesis of TNBC and could contribute to the develop- outcome due to the lack of beneficial therapeutic targets. To ment of molecular targets as a treatment for TNBC patients. clarify the molecular mechanisms involved in the carcino- genesis of TNBC and to identify target molecules for novel Introduction anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were Breast cancer is one of the most common solid malignant purified by laser-microbeam microdissection. We identified tumors among women worldwide. Breast cancer is a heteroge- 301 and 321 transcripts that were significantly upregulated neous disease that is currently classified based on the expression and downregulated in TNBC, respectively.