kinetochores

Summary

Summary: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.

Top Publications

  1. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
  2. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
  3. ncbi Un ménage à quatre: the molecular biology of chromosome segregation in meiosis
    Mark Petronczki
    Research Institute of Molecular Pathology, Dr Bohrgasse 7, 1030 Vienna, Austria
    Cell 112:423-40. 2003
  4. doi The spindle assembly checkpoint
    Pablo Lara-Gonzalez
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    Curr Biol 22:R966-80. 2012
  5. pmc CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold
    Tatsuya Nishino
    Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies SOKENDAI, Mishima, Shizuoka 411 8540, Japan
    Cell 148:487-501. 2012
  6. pmc The life and miracles of kinetochores
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 28:2511-31. 2009
  7. pmc In vitro centromere and kinetochore assembly on defined chromatin templates
    Annika Guse
    Department of Biochemistry, Stanford Medical School, Beckman 409A, Stanford, California 94305 5307, USA
    Nature 477:354-8. 2011
  8. pmc Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    J Cell Biol 190:73-87. 2010
  9. pmc Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface
    Julie P I Welburn
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell 38:383-92. 2010
  10. doi Polo on the Rise-from Mitotic Entry to Cytokinesis with Plk1
    Mark Petronczki
    Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, United Kingdom
    Dev Cell 14:646-59. 2008

Detail Information

Publications311 found, 100 shown here

  1. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
    ..These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer...
  2. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
    ..Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores--structures that mediate the binding of spindle microtubules to chromosomes in mitosis...
  3. ncbi Un ménage à quatre: the molecular biology of chromosome segregation in meiosis
    Mark Petronczki
    Research Institute of Molecular Pathology, Dr Bohrgasse 7, 1030 Vienna, Austria
    Cell 112:423-40. 2003
    ....
  4. doi The spindle assembly checkpoint
    Pablo Lara-Gonzalez
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    Curr Biol 22:R966-80. 2012
    ..Accuracy requires that chromosomes become correctly attached to the microtubule spindle apparatus via their kinetochores. When not correctly attached to the spindle, kinetochores activate the spindle assembly checkpoint network, ..
  5. pmc CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold
    Tatsuya Nishino
    Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies SOKENDAI, Mishima, Shizuoka 411 8540, Japan
    Cell 148:487-501. 2012
    ..These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the "histone code" beyond canonical nucleosome proteins...
  6. pmc The life and miracles of kinetochores
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 28:2511-31. 2009
    b>Kinetochores are large protein assemblies built on chromosomal loci named centromeres. The main functions of kinetochores can be grouped under four modules...
  7. pmc In vitro centromere and kinetochore assembly on defined chromatin templates
    Annika Guse
    Department of Biochemistry, Stanford Medical School, Beckman 409A, Stanford, California 94305 5307, USA
    Nature 477:354-8. 2011
    ..b>Kinetochores are assembled on a specialized chromatin domain called the centromere, which is characterized by the ..
  8. pmc Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    J Cell Biol 190:73-87. 2010
    ..Mad1 and the ROD-ZWILCH-ZW10 complex, both of which are important for the spindle checkpoint, from unattached kinetochores. By using reversine, we also demonstrate that MPS1 is required for the correction of improper chromosome-..
  9. pmc Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface
    Julie P I Welburn
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell 38:383-92. 2010
    Accurate chromosome segregation requires carefully regulated interactions between kinetochores and microtubules, but how plasticity is achieved to correct diverse attachment defects remains unclear...
  10. doi Polo on the Rise-from Mitotic Entry to Cytokinesis with Plk1
    Mark Petronczki
    Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, United Kingdom
    Dev Cell 14:646-59. 2008
    ..In this review, we focus on how Plk1 is recruited to centrosomes, kinetochores, and the spindle midzone and what the specific tasks of Plk1 at these distinct subcellular structures might be...
  11. pmc Epigenetic regulation of centromeric chromatin: old dogs, new tricks?
    Robin C Allshire
    Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, 6 34 Swann Building, Mayfield Road, Edinburgh EH9 3JR, UK
    Nat Rev Genet 9:923-37. 2008
    ..The establishment and maintenance of centromeric chromatin, and therefore the location of kinetochores, is epigenetically regulated...
  12. ncbi Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I
    Kirsten P Rabitsch
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Dev Cell 4:535-48. 2003
    ..here the identification of a protein complex, Csm1/Lrs4, that is essential for monoorientation of sister kinetochores in Saccharomyces cerevisiae. Both proteins are present in vegetative cells, where they reside in the nucleolus...
  13. doi Two histone marks establish the inner centromere and chromosome bi-orientation
    Yuya Yamagishi
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Science 330:239-43. 2010
    ..chromosomal passenger complex (CPC) including Aurora B and survivin must be localized at the center of paired kinetochores, at the site called the inner centromere...
  14. pmc Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis
    Fangwei Wang
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Harvard Medical School, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Science 330:231-5. 2010
    ..Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora B during mitosis...
  15. pmc Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells
    William T Silkworth
    Virginia Tech, Department of Biological Sciences, Blacksburg, VA, USA
    PLoS ONE 4:e6564. 2009
    ..We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells...
  16. pmc Mechanisms of chromosomal instability
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 20:R285-95. 2010
    ..Understanding these mechanisms provides insight into the cellular consequences of CIN and reveals the possibility of exploiting CIN in cancer therapy...
  17. pmc The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments
    Jens C Schmidt
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Dev Cell 23:968-80. 2012
    ..How kinetochores associate with depolymerizing microtubules, which undergo dramatic structural changes forming curved ..
  18. pmc Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore
    Jan H Bergmann
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland, UK
    EMBO J 30:328-40. 2011
    b>Kinetochores assemble on distinct 'centrochromatin' containing the histone H3 variant CENP-A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2)...
  19. doi The ABCs of CENPs
    Marinela Perpelescu
    Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka, Japan
    Chromosoma 120:425-46. 2011
    ..This review presents discussion of the latest structural and functional data on CENP-A and CENPs from the CCAN as well as their interaction with the KMN network...
  20. ncbi Scm3 is essential to recruit the histone h3 variant cse4 to centromeres and to maintain a functional kinetochore
    Raymond Camahort
    The Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA
    Mol Cell 26:853-65. 2007
    ..In addition, Scm3 is required to maintain kinetochore function throughout the cell cycle. We propose a model in which Ndc10/Scm3 binds to centromeric DNA, which is in turn essential for targeting Cse4 to centromeres...
  21. pmc The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly
    Tetsuya Hori
    Department of Molecular Genetics, National Institute of Genetics, Mishima, Shizuoka 411 8540, Japan
    J Cell Biol 200:45-60. 2013
    ..Using this system, we created two distinct types of engineered kinetochores, both of which were stably maintained in chicken DT40 cells...
  22. pmc The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly
    Valentin Magidson
    Wadsworth Center, New York State Department of Health, Albany, NY 12201 509, USA
    Cell 146:555-67. 2011
    Error-free chromosome segregation requires stable attachment of sister kinetochores to the opposite spindle poles (amphitelic attachment). Exactly how amphitelic attachments are achieved during spindle assembly remains elusive...
  23. pmc Point centromeres contain more than a single centromere-specific Cse4 (CENP-A) nucleosome
    Josh Lawrimore
    Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 195:573-82. 2011
    Cse4 is the budding yeast homologue of CENP-A, a modified histone H3 that specifies the base of kinetochores in all eukaryotes. Budding yeast is unique in having only one kinetochore microtubule attachment site per centromere...
  24. pmc The Ndc80 kinetochore complex forms oligomeric arrays along microtubules
    Gregory M Alushin
    Biophysics Graduate Group, University of California, Berkeley, California 94720, USA
    Nature 467:805-10. 2010
    ..The complex's mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing kinetochore-microtubule attachments...
  25. pmc A super-resolution map of the vertebrate kinetochore
    Susana Abreu Ribeiro
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK
    Proc Natl Acad Sci U S A 107:10484-9. 2010
    ..with deconvolution and super-resolution fluorescence microscopy for a detailed structural analysis of chicken kinetochores. Using fluorescence microscopy with subdiffraction spatial resolution and single molecule sensitivity to map ..
  26. doi CENP-C is a structural platform for kinetochore assembly
    Marcin R Przewloka
    Department of Genetics, University of Cambridge, Cambridge, UK
    Curr Biol 21:399-405. 2011
    Centromeres provide a region of chromatin upon which kinetochores are assembled in mitosis...
  27. pmc The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics
    Shinya Ohta
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK
    Cell 142:810-21. 2010
    ..Our integrated analysis predicts that up to 97 new centromere-associated proteins remain to be discovered in our data set...
  28. pmc Sensing centromere tension: Aurora B and the regulation of kinetochore function
    Michael A Lampson
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Trends Cell Biol 21:133-40. 2011
    ..To ensure that daughter cells inherit the correct chromosomes, the sister kinetochores must attach to opposite spindle poles...
  29. doi CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint
    Violeta Morin
    Universite Montpellier, CRBM, 34293 Montpellier, France
    Curr Biol 22:289-95. 2012
    ..Constitutive phosphorylation of S283 lowers the number of kinetochores required to hold the checkpoint, which suggests that CDK-dependent phosphorylation of MPS1 is essential to ..
  30. pmc Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes
    Liming Gui
    Cell and Developmental Biology, University College London, London WC1E 6BT, UK
    Development 139:1941-6. 2012
    ..The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition...
  31. pmc Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes
    Karen E Gascoigne
    Whitehead Institute for Biomedical Research, Department of Biology, Nine Cambridge Center, MA 02142, USA
    Cell 145:410-22. 2011
    ..We additionally find that CENP-T phosphorylation regulates the mitotic assembly of both endogenous and ectopic kinetochores. Thus, CENP-C and CENP-T form a critical regulated platform for vertebrate kinetochore assembly.
  32. pmc Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex
    Laura Hewitt
    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 190:25-34. 2010
    ..When Mps1 is inhibited before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished...
  33. pmc Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase
    Emily A Foley
    Laboratory of Chemistry and Cell Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nat Cell Biol 13:1265-71. 2011
    ..Consistent with this, multiple kinases, including Aurora B and Plk1, are enriched at kinetochores of mal-oriented chromosomes when compared with bi-oriented chromosomes, which have stable attachments...
  34. doi Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes
    Tomoya S Kitajima
    Cell Biology and Biophysics Unit, European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, Heidelberg D 69117, Germany
    Cell 146:568-81. 2011
    ..Our analysis reveals the error-prone nature of homologous chromosome biorientation, providing a possible explanation for the high incidence of aneuploid eggs observed in mammals, including humans...
  35. pmc Pericentromeric sister chromatid cohesion promotes kinetochore biorientation
    Tessie M Ng
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Mol Biol Cell 20:3818-27. 2009
    Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles...
  36. pmc The roles of microtubule-based motor proteins in mitosis: comprehensive RNAi analysis in the Drosophila S2 cell line
    Gohta Goshima
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107, USA
    J Cell Biol 162:1003-16. 2003
    ..From our phenotypic data, we construct a model for the distinct roles of molecular motors during mitosis in a single metazoan cell type...
  37. pmc Breaking the HAC Barrier: histone H3K9 acetyl/methyl balance regulates CENP-A assembly
    Jun Ichirou Ohzeki
    Department of Human Genome Research, Laboratory of Cell Engineering, Kazusa DNA Research Institute, Kisarazu, Chiba, Japan
    EMBO J 31:2391-402. 2012
    The kinetochore is responsible for accurate chromosome segregation. However, the mechanism by which kinetochores assemble and are maintained remains unclear...
  38. pmc Centromeres: unique chromatin structures that drive chromosome segregation
    Jolien S Verdaasdonk
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Rev Mol Cell Biol 12:320-32. 2011
    ....
  39. pmc Fission yeast Scm3: A CENP-A receptor required for integrity of subkinetochore chromatin
    Alison L Pidoux
    Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, 6 34 Swann Building, Edinburgh EH93JR, Scotland, UK
    Mol Cell 33:299-311. 2009
    ....
  40. pmc Tension directly stabilizes reconstituted kinetochore-microtubule attachments
    Bungo Akiyoshi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Nature 468:576-9. 2010
    b>Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes...
  41. ncbi The Ipl1-Aurora protein kinase activates the spindle checkpoint by creating unattached kinetochores
    Benjamin A Pinsky
    Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, PO Box 19024, Seattle, WA 98109, USA
    Nat Cell Biol 8:78-83. 2006
    ..spindle checkpoint ensures accurate chromosome segregation by delaying cell-cycle progression until all sister kinetochores capture microtubules from opposite poles and come under tension (for reviews, see refs 1, 2)...
  42. pmc The CENP-S complex is essential for the stable assembly of outer kinetochore structure
    Miho Amano
    Department of Molecular Genetics, National Institute of Genetics, The Graduate University for Advanced Studies, Mishima, Shizuoka 411 8540, Japan
    J Cell Biol 186:173-82. 2009
    ..In addition, we found that intrakinetochore distance was increased in CENP-S- and CENP-X-deficient cells. These results suggest that the CENP-S complex is essential for the stable assembly of the outer kinetochore...
  43. pmc CENP-A exceeds microtubule attachment sites in centromere clusters of both budding and fission yeast
    Valerie C Coffman
    Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 195:563-72. 2011
    The stoichiometries of kinetochores and their constituent proteins in yeast and vertebrate cells were determined using the histone H3 variant CENP-A, known as Cse4 in budding yeast, as a counting standard...
  44. pmc Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment
    Toyoaki Natsume
    Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Mol Cell 50:661-74. 2013
    ..Here, we show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex...
  45. pmc Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores
    Nitobe London
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Curr Biol 22:900-6. 2012
    b>Kinetochores are the macromolecular complexes that interact with microtubules to mediate chromosome segregation. Accurate segregation requires that kinetochores make bioriented attachments to microtubules from opposite poles...
  46. pmc Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint
    Lindsey A Shepperd
    Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK
    Curr Biol 22:891-9. 2012
    ..Checkpoint proteins are recruited to kinetochores when individual kinetochores are not bound to spindle microtubules or not under tension...
  47. doi Drosophila CENH3 is sufficient for centromere formation
    María José Mendiburo
    Max Planck Institute of Immunobiology, Stubeweg 51, 79108 Freiburg, Germany
    Science 334:686-90. 2011
    ..We conclude that CID is both necessary and sufficient to serve as an epigenetic centromere mark and nucleate heritable centromere function...
  48. doi MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components
    Yuya Yamagishi
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Nat Cell Biol 14:746-52. 2012
    ..The spindle assembly checkpoint (SAC) senses unattached kinetochores and prevents premature entry to anaphase, thus ensuring that all chromosomes attach to opposite spindle poles (..
  49. pmc Mouse centric and pericentric satellite repeats form distinct functional heterochromatin
    Mounia Guenatri
    Institut Curie Research section, UMR218 du Centre National pour la Recherche Scientifique, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    J Cell Biol 166:493-505. 2004
    ..Thus, we define functionally independent centromeric subdomains, which spatio-temporal isolation is proposed to be important for centromeric cohesion and dissociation during chromosome segregation...
  50. pmc Quantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunit
    Bungo Akiyoshi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genes Dev 23:2887-99. 2009
    ..When sister kinetochores make bioriented attachments to microtubules from opposite poles, the spindle checkpoint is silenced...
  51. pmc Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells
    Prashant K Mishra
    Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 7:e1002303. 2011
    ..conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast...
  52. pmc Chromosome missegregation in human cells arises through specific types of kinetochore-microtubule attachment errors
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 108:17974-8. 2011
    ..Chromosomes with merotelic kinetochores often manifest as lagging chromosomes in anaphase, suggesting that lagging chromosomes fail to segregate ..
  53. pmc Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis
    Markus Posch
    Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 191:61-74. 2010
    ..Sds22 is required for proper progression through mitosis and localization of PP1 to mitotic kinetochores. Depletion of Sds22 increases aurora B T-loop phosphorylation and the rate of recovery from monastrol arrest...
  54. pmc Spindle assembly checkpoint: the third decade
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy
    Philos Trans R Soc Lond B Biol Sci 366:3595-604. 2011
    ..the discovery that the Ndc80 complex and other components of the microtubule-binding interface of kinetochores are essential for the checkpoint response finally asserted that kinetochores are crucial for the checkpoint ..
  55. pmc Tripartite organization of centromeric chromatin in budding yeast
    Kristina Krassovsky
    Basic Sciences Division, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 109:243-8. 2012
    ....
  56. pmc Active transcription and essential role of RNA polymerase II at the centromere during mitosis
    F Lyn Chan
    Chromosome and Chromatin Research, Department of Paediatrics, Murdoch Childrens Research Institute, Royal Children s Hospital, University of Melbourne, Parkville, Victoria 3052, Australia
    Proc Natl Acad Sci U S A 109:1979-84. 2012
    ..These findings demonstrate an essential role of RNAPII in the transcription of α-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore...
  57. pmc Structural organization of the kinetochore-microtubule interface
    Jennifer G DeLuca
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, United States
    Curr Opin Cell Biol 24:48-56. 2012
    ..Here, we review important recent advancements and discuss several unresolved questions regarding how kinetochores dynamically bridge mitotic chromosomes to spindle microtubules.
  58. pmc Centromeric nucleosomes induce positive DNA supercoils
    Takehito Furuyama
    Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cell 138:104-13. 2009
    ..The mutual incompatibility of nucleosomes with opposite topologies could explain how centromeres are efficiently maintained as unique loci on chromosomes...
  59. pmc Centromere identity is specified by a single centromeric nucleosome in budding yeast
    Suzanne Furuyama
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 104:14706-11. 2007
    ..Therefore, a single CenH3 nucleosome forms the minimal unit of centromeric chromatin necessary for kinetochore assembly and proper chromosome segregation...
  60. pmc Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore
    Emanuela Screpanti
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Curr Biol 21:391-8. 2011
    b>Kinetochores are proteinaceous scaffolds implicated in the formation of load-bearing attachments of chromosomes to microtubules during mitosis...
  61. ncbi Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I
    Rosemary K Clyne
    Research Institute of Molecular Pathology IMP, Vienna A 1030, Austria
    Nat Cell Biol 5:480-5. 2003
    ..Second, sister kinetochores attach to microtubules from the same pole (mono-polar orientation), causing maternal and paternal centromere ..
  62. pmc Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference
    Changjun Zhu
    The Burnham Institute, La Jolla, CA 92037, USA
    Mol Biol Cell 16:3187-99. 2005
    ..Using immunofluorescence analysis, time-lapse microscopy, and rescue experiments, we investigate the roles of these 12 kinesins in detail...
  63. ncbi The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint
    Anna De Antoni
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy
    Curr Biol 15:214-25. 2005
    ..In prometaphase, Mad2 is recruited to kinetochores with the help of Mad1, and it is activated to bind Cdc20...
  64. ncbi Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation
    Brian H Lee
    Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, E17 233, 40 Ames Street, Cambridge, MA 02139, USA
    Science 300:482-6. 2003
    ..Furthermore, in the absence of CDC5 kinetochores were bioriented during meiosis I, and Mam1, a protein essential for coorientation, failed to associate with ..
  65. pmc Dynamics of inner kinetochore assembly and maintenance in living cells
    Peter Hemmerich
    Leibniz Institute for Age Research, Fritz Lipmann Institute, 07745 Jena, Germany i leibniz de
    J Cell Biol 180:1101-14. 2008
    ..Our data reveal a wide range of cell cycle-specific assembly plasticity of the centromere that provides both stability through sustained binding of some components and flexibility through dynamic exchange of other components...
  66. pmc Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    EMBO J 30:1508-19. 2011
    ..Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways...
  67. pmc Tension sensing by Aurora B kinase is independent of survivin-based centromere localization
    Christopher S Campbell
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA
    Nature 497:118-21. 2013
    ..under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments...
  68. ncbi PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint
    Christoph Baumann
    Department of Cell Biology, Max Planck Institute of Biochemistry, D 82152 Martinsried, Germany
    Cell 128:101-14. 2007
    ..Starting in prometaphase, PICH accumulates at kinetochores and inner centromeres...
  69. pmc Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint
    Daniela A Brito
    Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York 12222, USA
    Curr Biol 16:1194-200. 2006
    In the presence of unattached/weakly attached kinetochores, the spindle assembly checkpoint (SAC) delays exit from mitosis by preventing the anaphase-promoting complex (APC)-mediated proteolysis of cyclin B, a regulatory subunit of cyclin-..
  70. pmc Pericentric chromatin is organized into an intramolecular loop in mitosis
    Elaine Yeh
    Department of Biology, 623 Fordham Hall CB 3280, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 3280, USA
    Curr Biol 18:81-90. 2008
    ..Cohesin is concentrated at the centromere region of the chromosome despite the fact that sister centromeres can be separated by 800 nm in vivo. The function of cohesin at sites of separated DNA is unknown...
  71. pmc Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores
    Claire Ditchfield
    School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Rd, Manchester M13 9PT, UK
    J Cell Biol 161:267-80. 2003
    ..Furthermore, inhibition of Aurora B kinase activity prevents the rebinding of BubR1 to metaphase kinetochores after a reduction in centromeric tension...
  72. ncbi Molecular architecture of the kinetochore-microtubule interface
    Iain M Cheeseman
    Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 9:33-46. 2008
    ..Recent studies have identified more than 80 kinetochore components, and are revealing how these proteins are organized into the higher order kinetochore structure, as well as how they function to achieve proper chromosome segregation...
  73. ncbi Identification of cohesin association sites at centromeres and along chromosome arms
    T Tanaka
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 98:847-58. 1999
    ..Finally, cohesion associated with "minimal" centromeres is insufficient to resist the splitting force exerted by microtubules and appears to be reinforced by cohesion provided by their flanking DNA sequences...
  74. pmc KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint
    Jessica S Rosenberg
    Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA
    Curr Biol 21:942-7. 2011
    The spindle assembly checkpoint (SAC) delays anaphase onset until kinetochores accomplish bioriented microtubule attachments [1]...
  75. pmc Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E
    Yumi Kim
    Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 142:444-55. 2010
    ..b>Kinetochores on such chromosomes cannot make subsequent stable attachment to spindle microtubules when dephosphorylation of ..
  76. pmc In vivo protein architecture of the eukaryotic kinetochore with nanometer scale accuracy
    Ajit P Joglekar
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Curr Biol 19:694-9. 2009
    ..the core structure of the budding yeast kinetochore reported here is remarkably similar to that found in mammalian kinetochores, indicating that kinetochore structure is conserved in eukaryotes with either point or regional centromeres.
  77. pmc HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore
    Meghan C Barnhart
    Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA
    J Cell Biol 194:229-43. 2011
    ....
  78. doi Tracking spindle checkpoint signals from kinetochores to APC/C
    Luying Jia
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA
    Trends Biochem Sci 38:302-11. 2013
    ..At metaphase, spindle microtubules from opposing spindle poles capture each pair of sister kinetochores, exert pulling forces, and create tension across sister kinetochores...
  79. pmc Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore
    Julien Espeut
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USA
    J Cell Biol 196:469-82. 2012
    ..We propose that microtubule binding by KNL-1 functions in checkpoint silencing by sensing microtubules attached to kinetochores and relaying their presence to eliminate generation of the checkpoint signal.
  80. pmc The kinetochore proteins Pcs1 and Mde4 and heterochromatin are required to prevent merotelic orientation
    Juraj Gregan
    Max F Perutz Laboratories, Department of Chromosome Biology, University of Vienna, Dr Bohr Gasse 1, 1030 Vienna, Austria
    Curr Biol 17:1190-200. 2007
    ..A protein called Pcs1 has been implicated in preventing merotelic attachment in mitosis and meiosis II in the fission yeast S. pombe...
  81. pmc Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function
    Jan H Bergmann
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, King s Building, Mayfield Road, Edinburgh EH9 3JR, UK
    J Cell Sci 125:411-21. 2012
    Human kinetochores are transcriptionally active, producing very low levels of transcripts of the underlying alpha-satellite DNA...
  82. doi Molecular architecture of vertebrate kinetochores
    Kozo Takeuchi
    Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka 411 8540, Japan
    Exp Cell Res 318:1367-74. 2012
    b>Kinetochores form a dynamic interface with the microtubules from the mitotic spindle to achieve accurate chromosome segregation. Multiple proteins are assembled on centromeric DNA to form the kinetochore structure...
  83. pmc Deviant kinetochore microtubule dynamics underlie chromosomal instability
    Samuel F Bakhoum
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 19:1937-42. 2009
    The persistent malattachment of microtubules to chromosomes at kinetochores is a major mechanism of chromosomal instability (CIN) [1, 2]...
  84. pmc The NDC80 complex proteins Nuf2 and Hec1 make distinct contributions to kinetochore-microtubule attachment in mitosis
    Lynsie J R Sundin
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA
    Mol Biol Cell 22:759-68. 2011
    Successful mitosis requires that kinetochores stably attach to the plus ends of spindle microtubules. Central to generating these attachments is the NDC80 complex, made of the four proteins Spc24, Spc25, Nuf2, and Hec1/Ndc80...
  85. doi Heterochromatin integrity affects chromosome reorganization after centromere dysfunction
    Kojiro Ishii
    Division of Cell Biology, Institute of Life Science, Kurume University, Japan
    Science 321:1088-91. 2008
    ..By affecting the modes of chromosomal reorganization, the genomic distribution of heterochromatin may influence the fate of karyotype evolution...
  86. pmc Overlapping regulation of CenH3 localization and histone H3 turnover by CAF-1 and HIR proteins in Saccharomyces cerevisiae
    Jessica Lopes da Rosa
    Department of Molecular and Cell Biology, University of California, Berkeley, California 947202, USA
    Genetics 187:9-19. 2011
    ..We discuss ways in which altered histone exchange kinetics may affect eviction of Cse4 from noncentromeric loci...
  87. pmc Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment
    Lina Cheng
    Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Dev Cell 20:342-52. 2011
    Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment...
  88. pmc Condensin regulates the stiffness of vertebrate centromeres
    Susana A Ribeiro
    Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom
    Mol Biol Cell 20:2371-80. 2009
    ..bioriented at metaphase, the elastic stretch of centromeric chromatin opposes pulling forces exerted on sister kinetochores by the mitotic spindle...
  89. doi Condensin association with histone H2A shapes mitotic chromosomes
    Kenji Tada
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Nature 474:477-83. 2011
    ..Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear...
  90. pmc Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction
    Veronica Krenn
    Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy
    J Cell Biol 196:451-67. 2012
    The function of the essential checkpoint kinases Bub1 and BubR1 requires their recruitment to mitotic kinetochores. Kinetochore recruitment of Bub1 and BubR1 is proposed to rely on the interaction of the tetratricopeptide repeats (TPRs) ..
  91. pmc Aurora B kinase controls the targeting of the Astrin-SKAP complex to bioriented kinetochores
    Jens C Schmidt
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    J Cell Biol 191:269-80. 2010
    During mitosis, kinetochores play multiple roles to generate interactions with microtubules, and direct chromosome congression, biorientation, error correction, and anaphase segregation...
  92. pmc Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation
    Maria Maldonado
    Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York 10065, USA
    Nat Cell Biol 13:475-82. 2011
    ..models, the recruitment of the spindle-assembly checkpoint protein Mad2, through Mad1, to non-bioriented kinetochores is needed to stop cell-cycle progression...
  93. pmc Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors
    John C Meadows
    Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK
    Dev Cell 20:739-50. 2011
    ..These data demonstrate that at least two distinct pools of PP1, one kinetochore associated and the other motor associated, are needed to silence the spindle checkpoint...
  94. pmc Temporal changes in Hec1 phosphorylation control kinetochore-microtubule attachment stability during mitosis
    Keith F Deluca
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA
    J Cell Sci 124:622-34. 2011
    Precise control of the attachment strength between kinetochores and spindle microtubules is essential to preserve genomic stability...
  95. doi The kinetochore and the centromere: a working long distance relationship
    Marcin R Przewloka
    University of Cambridge, Department of Genetics, Cambridge, CB2 3EH, United Kingdom
    Annu Rev Genet 43:439-65. 2009
    ....
  96. pmc Mechanisms of force generation by end-on kinetochore-microtubule attachments
    Ajit P Joglekar
    Department of Biology, University of North Carolina, Chapel Hill, NC 27599 3280, United States
    Curr Opin Cell Biol 22:57-67. 2010
    ..We briefly discuss potential contributions of motors, other microtubule-associated proteins, and microtubule depolymerases. Using the above evidence, we present speculative models of force generation at the kinetochore...
  97. pmc The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores
    Ram Kumar Mishra
    Laboratory of Gene Regulation and Development, NICHD NIH, Bethesda, MD 20892, USA
    Nat Cell Biol 12:164-9. 2010
    ..pore complex (NPC) disassembles during mitosis, and many of its constituents distribute onto spindles and kinetochores, including the Nup107-160 sub-complex...
  98. pmc Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling
    John Maciejowski
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Cell Biol 190:89-100. 2010
    ..e., before the appearance of functional kinetochores. Furthermore, intramitotic Mps1 inhibition evicted Bub1 and all other known SAC transducers from the outer ..
  99. ncbi Nuclear envelope breakdown proceeds by microtubule-induced tearing of the lamina
    Joel Beaudouin
    Gene Expression and Cell Biology Biophysics Programmes, European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
    Cell 108:83-96. 2002
    ..NE fragments remaining on chromosomes were removed toward the centrosomes in a microtubule-dependent manner, suggesting a mechanism mediated by a minus-end-directed motor...
  100. pmc Molecular control of kinetochore-microtubule dynamics and chromosome oscillations
    Ana C Amaro
    Institute of Biochemistry, Eidgenossische Technische Hochschule ETH Zurich, CH 8093 Zurich, Switzerland
    Nat Cell Biol 12:319-29. 2010
    Chromosome segregation in metazoans requires the alignment of sister kinetochores on the metaphase plate...
  101. pmc The MIS12 complex is a protein interaction hub for outer kinetochore assembly
    Arsen Petrovic
    Department of Experimental Oncology, European Institute of Oncology IEO, Milan, Italy
    J Cell Biol 190:835-52. 2010
    b>Kinetochores are nucleoprotein assemblies responsible for the attachment of chromosomes to spindle microtubules during mitosis...

Research Grants62

  1. Centromere Structure and Function in Candida albicans
    Judith G Berman; Fiscal Year: 2012
    ..Centromeres (CENs) are the DNA regions where proteins assemble to form kinetochores, the structures that tether chromosomes to the mitotic spindle...
  2. Assembly and Maintenance of Centromeres in Filamentous Fungi
    Michael Freitag; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Centromeres form the foundation of kinetochores, the attachment points for spindle microtubules that transport chromosomes into daughter nuclei during nuclear division...
  3. Molecular Analysis of Pericentric Sister Chromatid Cohesion
    PAUL CONNOR MEGEE; Fiscal Year: 2013
    ..We showed previously that budding yeast kinetochores direct pericentromeric cohesin domain assembly...
  4. Kinetochore Function and Cell Cycle Progression Revision
    Katsumi Kitagawa; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Basic studies of genes required for the function of kinetochores and the surveillance of the spindle checkpoint are directly relevant to cancer research...
  5. Homolog orientation and segregation in acentrosomal meiosis
    Kim S McKim; Fiscal Year: 2013
    ..In cells with centrosomes, the microtubule connections formed between the poles and the kinetochores facilitates bi-orientation of sisters (mitosis) or homologous chromosomes (meiosis I)...
  6. Age and molecular mechanisms contributing to aneuploidy in oocytes
    Richard M Schultz; Fiscal Year: 2013
    ..Another process that prevents errors is regulation of connections between kinetochores and spindle microtubules that results in a spindle with chromosomes correctly attached...
  7. Regulation of cell division in Trypanosoma brucei
    Ziyin Li; Fiscal Year: 2011
    ..bodies as the microtubule organizing centers for mitotic spindle assembly and there are insufficient numbers of kinetochores per chromosomes (Ogbadoyi et al., 2000)...
  8. A Molecular View of Chromosome Recombination &Segregation in Eukaryotic Meiosis
    KEVIN DANIEL CORBETT; Fiscal Year: 2013
    ..We will first study the S. cerevisiae monopolin complex, which binds chromosomes'kinetochores in meiosis I and modifies their attachments to spindle microtubules, to enable the proper orientation and ..
  9. Molecular Mechanisms of Chromosome Segregation in Yeast
    Jennifer L Gerton; Fiscal Year: 2012
    ..will explore the molecular mechanisms of chromosome segregation with particular attention to centromeres and kinetochores. Centromeres are cis acting sequences on chromosomes that are required for their correct segregation...
  10. Regulation of Chromosome Segregation
    SUSAN BIGGINS; Fiscal Year: 2013
    ..forces generated by spindle microtubules that are translated into chromosome movement through interactions with kinetochores, the highly conserved structures that assemble onto centromeric chromatin...
  11. Kinetochore-Microtubule Interactions
    JOHN RICHARD MCINTOSH; Fiscal Year: 2012
    ..Proper mitosis, in turn, depends on correct interactions between kinetochores and spindle microtubules...
  12. Chromatin maintenance and sister chromatid differentiation
    Peter M Lansdorp; Fiscal Year: 2013
    ..be involved in cell fate regulation if microtubules originating from "mother'centrosomes were to prefer kinetochores present on just one of the two sister chromatids of specific chromosomes...
  13. Dissection of the Inner Centromere Regulatory Network
    P Todd Stukenberg; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): For each chromosome to properly segregate during mitosis, its kinetochores must bipolarly attach spindle microtubules...
  14. Molecular Architecture of the Regional Kinetochore in Fission Yeast
    Xiangwei He; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Kinetochores are specialized protein complexes that are assembled on specific loci of chromosomes named centromeres...
  15. Regulation of Centromeric Chromatin
    SUSAN BIGGINS; Fiscal Year: 2013
    ..Chromosomes segregate using their kinetochores, the specialized protein structures that assemble on centromeric DNA sequences and mediate attachment to ..
  16. MICROTUBULE REGULATION
    Don W Cleveland; Fiscal Year: 2013
    ..This requires attachment of spindle microtubules to kinetochores, specialized structures formed at centromeres...
  17. SACCHAROMYCES CEREVISIAE MICROTUBULE CYTOSKELETON
    Georjana Barnes; Fiscal Year: 2013
    ..or about emergent properties that result when separate subcomplexes like Dam1 and Ndc80 are together in kinetochores. Building upon discovery and analysis of the Dam1 complex, and structure studies of the Ndc80 complex, new ..
  18. Centrosome and mitotic functions of ciliary proteins
    Stephen Doxsey; Fiscal Year: 2009
    ..IFT proteins localize to spindle poles as well as kinetochores, midbodies and spindle microtubules...
  19. FEEDBACK CONTROL OF THE CELL CYCLE
    Andrew W Murray; Fiscal Year: 2013
    ..Experiments are proposed to: 1) Use natural and synthetic kinetochores to dissect the interaction of chromosomes and microtubules that create the mitotic spindle...
  20. The Mechanism of Spindle Assembly Checkpoint Control in DNA Damage Response
    Yuko Nakajima; Fiscal Year: 2013
    ..In animals, SAC proteins have been found at some kinetochores upon DNA damage, however how SAC is controlled in DNA damage response is unknown...
  21. Roles of chromosomal factors in chromosome segregation
    Hironori Funabiki; Fiscal Year: 2013
    ..the CC domain will be systematically modulated, and changes in Aurora B-dependent phosphorylation within kinetochores will be monitored...
  22. Microtubule Complexes Involved in Intracelluar Transport
    Ronald D Vale; Fiscal Year: 2013
    ..We have also identified a new protein that may regulate dynein at kinetochores, and we will pursue further studies of this protein...
  23. Computer Integrated Systems for Microscopy and Manipulation
    Richard Superfine; Fiscal Year: 2013
    ..organize the chromosomes along the midplate, sensing forces to pass through the checkpoint to finally pull the kinetochores poleward with polymerization forces...
  24. Determining how the spindle assembly checkpoint monitors chromosome biorientation
    David Wynne; Fiscal Year: 2013
    ..properly, all replicated chromosomes must orient correctly on the mitotic spindle with each pair of sister kinetochores making attachments to microtubules from opposing spindle poles...
  25. FUNCTIONAL PROPERTIES OF CENTROSOMES IN SOMATIC CELLS
    Alexey L Khodjakov; Fiscal Year: 2013
    ..attachment is mediated by special macromolecular assemblies on the chromosome's body known as the 'kinetochores'...
  26. Mechanisms of Kinetochore Assembly
    Aaron F Straight; Fiscal Year: 2013
    ..Our long-term goal is to understand how centromeres and kinetochores are assembled to generate a microtubule-binding site that mediates chromosome segregation...
  27. Role of the Ndc80 Loop Domain and Cdt1 in Kinetochore Microtubule Attachments
    Dileep Varma; Fiscal Year: 2013
    ..to study how the microtubule (MT) motor protein Dynein, attaches to intracellular cargo like vesicles and kinetochores. My research on dynein function at kinetochores attracted me towards understanding the function of this ..
  28. High resolution electron cryo-microscope at Brandeis University.
    Nikolaus Grigorieff; Fiscal Year: 2009
    ..formin bound to regulators and growing actin filaments, viral cell entry, and the molecular organization of kinetochores. All of these projects address serious disorders associated with human disease, or the mechanism of prominent ..
  29. Coupling kinetochore microtubule dynamics to chromosome motion
    Ekaterina L Grishchuk; Fiscal Year: 2013
    ..crucially depends on the force- transducing interactions between thread-like polymers (microtubules), and kinetochores, specialized chromosomal structures: when microtubules shorten, the chromosomes are transported to the opposite ..
  30. Mechanisms of Spindle Assembly
    Claire E Walczak; Fiscal Year: 2012
    ..then performing a high-resolution fixed cell analysis in which we identify the locations of all chromosomes/ kinetochores in the spindle as well as measure the defects in the timing of mitotic progression, 2) Develop a new ..
  31. Mob1 Localization and Function During Mitosis
    Charles B Shuster; Fiscal Year: 2012
    ..human cells indicate that the localization dynamics mirror that observed in yeast, with Mob1 enriched at the kinetochores and spindle poles early in mitosis, and the spindle midzone and midbody during cytokinesis...
  32. Formin mDia Functions in Mitosis
    Yinghui Mao; Fiscal Year: 2013
    ..cultured cells and purified components in vitro, we intend to determine how formin mDia3 plays a novel role at kinetochores in contribute to stable microtubule attachment...
  33. BIOCHEMICAL AND GENETIC ANALYSIS OF YEAST KINETOCHORES
    PETER KARL SORGER; Fiscal Year: 2010
    b>Kinetochores are multi-protein complexes that assemble on centromeric (CEN) DMA and perform three essential functions in chromosome segregation (i) they bind paired sister chromatids to spindle microtubules (MTs) in a bipolar fashion ..
  34. MOLECULAR ANALYSIS OF THE SPINDLE POLE BODY
    Trisha N Davis; Fiscal Year: 2013
    ..Chromosomes attach to microtubules via kinetochores, multiprotein organelles that span from the DNA to the microtubule...
  35. CELL AND TUMOR GENETICS OF MITOTIC ARREST CHECKPOINTS
    PETER KARL SORGER; Fiscal Year: 2010
    ..Signals generated at kinetochores and transmitted via a transduction system comprised of Mad and Bub proteins, act to regulate the activity of ..
  36. Kinetochore Function in Vertebrate Cells
    Jennifer G DeLuca; Fiscal Year: 2013
    ..b>Kinetochores must also regulate the strength of this attachment, since incorrectly attached MTs must be released, and those ..
  37. Force generation and detection in the spindle: the case of the kinetochore
    Sophie Dumont; Fiscal Year: 2011
    ..The goal of the proposed research is to understand how mechanical force is generated on mammalian kinetochores and how it affects kinetochore motility and checkpoint chemistry...
  38. Mechano-molecular regulation of kinetochore function
    THOMAS JOSEPH MARESCA; Fiscal Year: 2013
    ..system and a spindle pole-based mechanism, each of which is impacted by forces that produce tension at kinetochores. The rationale underpinning the research is that determining the mechano-molecular basis of error correction ..
  39. MECHANISMS OF MICTOTIC SPINDLE ASSEMBLY AND FUNCTION
    Edward D Salmon; Fiscal Year: 2013
    ..b>Kinetochores have at least five key roles in assuring accurate segregation: 1) they produce a diffusible signal for the ..
  40. Structure and Function of Spindle Checkpoint Proteins
    Xuelian Luo; Fiscal Year: 2012
    ..In mitosis, the Mad1-Mad2 core complex recruits cytosolic Mad2 to kinetochores through Mad2 conformational dimerization and converts Mad2 to an intermediate conformer (I-Mad2) more amenable ..
  41. FORMATION,INTERACTION & FUNCTION OF SPINDLE COMPONENTS
    Conly L Rieder; Fiscal Year: 2010
    ..objectives of this proposal are to determine how entry and exit from mitosis is controlled, how centrosomes and kinetochores function and interact to form the spindle, and how the forces for chromosome motion &positioning are ..
  42. Mitotic functions of cilia proteins
    Stephen J Doxsey; Fiscal Year: 2013
    ..Other cilia proteins localize to additional mitotic structures such as kinetochores and midbodies, suggesting additional mitotic functions of this class of proteins...
  43. ORGANIZATION OF THE MAMMALIAN MITOTIC SPINDLE
    Duane A Compton; Fiscal Year: 2012
    ..will be on defining the molecules and mechanisms that govern the dynamic attachment of spindle microtubules to kinetochores. The specific aims of this research are to: 1) combine live cell imaging with quantitative chromosome ..
  44. Quantitative Measurements and Modeling of the Mitotic Checkpoint
    Jagesh V Shah; Fiscal Year: 2011
    ..By determining the array of signals produced by unattached kinetochores to prevent untimely chromosome segregation and the rates at which these are made we will be able to develop an ..
  45. Architecture-function analysis of the kinetochore motor
    Ajit Joglekar; Fiscal Year: 2013
    ..This work will establish a framework for building artificial kinetochores in cells.
  46. Multicolor TIRF microscope for studying mitotic spindle components at the single
    Charles L Asbury; Fiscal Year: 2010
    ..will study super-complexes assembled from pure, recombinant forms of the six protein subcomplexes that make up kinetochores to determine how their interactions allow kinetochores to link chromosomes to spindle microtubules...
  47. Role of Bub1 in SV40 large T antigen mediated transformation and replication
    Ole Gjoerup; Fiscal Year: 2011
    ..checkpoint, where it serves a critical function in monitoring tension and attachment at sister chromatid kinetochores. Bub1 is mutated in certain human cancers characterized by aneuploidy...
  48. Mechanisms of Mitotic Spindle Assembly
    LESLEY NICOLE WEAVER; Fiscal Year: 2013
    ..There are many proposed models for how the spindle assembles, however, the contributions of centrosomes, kinetochores, and chromatin to this process are not clearly defined...
  49. ATOMIC RESOLUTION IN BIOLOGICAL ELECTRON MICROSCOPY
    STEPHEN COPLAN HARRISON; Fiscal Year: 2013
    ..In pursuit of this theme, we will focus especially on the large-scale organization of dynamic structures such as kinetochores, cilia, and transport-vesicle tethering complexes.
  50. Biophysical study of reconstituted kinetochore-microtubule attachments
    Charles L Asbury; Fiscal Year: 2013
    b>Kinetochores are multiprotein organelles that orchestrate the movement of chromosomes during mitosis...
  51. Mechanisms of "End On" Microtubule Attachment by the Kinetochore
    P Todd Stukenberg; Fiscal Year: 2011
    b>Kinetochores are proteinaceous machines that coordinate numerous events during chromosome segregation, including moving chromosomes, generating spindle checkpoint signals and correcting improper microtubule attachments...
  52. Regulation of microtubule dynamics during cell division
    Ryoma Ohi; Fiscal Year: 2013
    ..Chromosomes engage microtubules in the mitotic spindle through specialized structures called kinetochores. Growth and shortening of kinetochore-microtubules generate forces that power chromosome movement...
  53. Induction of Cell Cleavage by the Mitotic Spindle
    Robert Margolis; Fiscal Year: 2009
    ..Passenger proteins are proteins that migrate from the kinetochores to the spindle equator during late mitosis and have a probable function in signaling the time and position of ..
  54. Reconstitution of the central-outer kinetochore interface
    Emily Mazanka; Fiscal Year: 2013
    ..Multi-component complexes called kinetochores link chromosomes to microtubules and serve as regulatory sites that sense when chromosomes are properly ..
  55. Investigate the molecular mechanism that ensures chromosome bipolar attachment
    Yanchang Wang; Fiscal Year: 2013
    ..Accurate chromosome segregation depends on the establishment of bipolar attachment, whereby sister kinetochores are attached to microtubules from opposite spindle poles...
  56. CENTROMERE STRUCTURE AND FUNCTION
    John Carbon; Fiscal Year: 2007
    ..valuable information gained in these groundwork studies, we will now extend the work to investigate centromere-kinetochores in the two most common and clinically significant pathogenic budding yeasts, Candida albicans and Candida ..
  57. Analysis of Loss of Function of MAD2 in Mammals
    Loren Michel; Fiscal Year: 2006
    ..The mitotic checkpoint delays mitosis at metaphase until the attachment of microtubules to the kinetochores is complete, allowing for equal segregation of chromosomes to the two daughter cells...
  58. The meiotic role of SIK19p in yeast
    Dean Dawson; Fiscal Year: 2005
    ..through meiosis I is accomplished by association of the chromatids at the centromere region and development of kinetochores that allow both chromatids to be moved as a unit to one pole of the spindle...
  59. FUNCTIONS OF CYTOPLASMIC DYNEIN
    J McIntosh; Fiscal Year: 1999
    ..studied in HeLa cells and rodent brain, is in the mitotic spindle, with concentrations on the centrosomes and kinetochores. During interphase, it is associated with cytoplasmic vesicles and perhaps with primary endosomes...
  60. PHOSPHOLIPASE C AND KINETOCHORE FUNCTION
    Ales Vancura; Fiscal Year: 2001
    ..2000) demonstrate that PLC in Saccharomyces cerevisiae (Plc1p protein encoded by the PLC1 gene) associates with kinetochores and affects their ability to bind microtubules...
  61. SISTER CHROMATID LINKAGE AND SEPARATION
    Andrew Murray; Fiscal Year: 2004
    ..Mitotic chromosome movements depend on kinetochores, which also act as signaling centers to delay anaphase until all the chromosomes have been correctly aligned on ..
  62. MICROTUBULE REGULATION
    Don Cleveland; Fiscal Year: 2003
    ..This is achieved by the attachment of spindle microtubules to kinetochores, specialized structures formed at centromeres...