title: A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint.
abstract: The COMA/CENP-H/I kinetochore complex regulates microtubule dynamics at kinetochores. The complex is also required to generate spindle checkpoint signals in both yeast and human cells under conditions where Aurora B activity is compromised. Our data explain why mammalian cells treated with Aurora inhibitors still have a functional spindle assembly checkpoint (SAC), since the checkpoint signals through CENP-H/I/N. The SAC effect from depleting the CENP-H/I/N complex cannot be explained by a weakened SAC signal, and the complex has no role in the SAC response to paclitaxel. We propose a model to explain the differential response of human cells to nocodazole and paclitaxel.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Matson
authors.forename: Pinar B
authors.initials: PB
authors.lastname: Demirel
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burke
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000502:physiology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: C121933:CENPH protein, human; C484297:CENPI protein, human; C571071:CENPN protein, human; C081874:CHL4 protein, S cerevisiae; C477822:CTF19 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C444703:Ctf3 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D050257:Tubulin Modulators; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel; D015739:Nocodazole