Human Condensin Function Is Essential for Centromeric Chromatin Assembly and Proper Sister Kinetochore Orientation
| Autor: | Ilia Ouspenski, Mary Dasso, James G. McNally, Alexander V. Strunnikov, Don W. Cleveland, Tatiana S. Karpova, Alexander Samoshkin, Louis Dye, Lars E.T. Jansen, Alexei Arnaoutov |
|---|---|
| Přispěvatelé: | Samoshkin, Alexander [0000-0001-6296-2254], Apollo - University of Cambridge Repository, Lichten, Michael |
| Rok vydání: | 2009 |
| Předmět: |
Chromosomal Proteins
Non-Histone Condensin Cell Biology/Cell Growth and Division Genetics and Genomics/Nuclear Structure and Function lcsh:Medicine Autoantigens Histones 0302 clinical medicine Aurora Kinases Aurora Kinase B lcsh:Science Adenosine Triphosphatases Microscopy 0303 health sciences Multidisciplinary biology Kinetochore Protein-Serine-Threonine Kinases Chromatin Cell biology Chromosomal Proteins Genetics and Genomics/Chromosome Biology DNA-Binding Proteins Cell Biology/Nuclear Structure and Function Research Article General Science & Technology Centromere Aurora B kinase Mitosis macromolecular substances Protein Serine-Threonine Kinases Electron Fluorescence 03 medical and health sciences Microscopy Electron Transmission Centromere Protein A Genetics Transmission Humans Amino Acid Sequence DNA Primers 030304 developmental biology Base Sequence lcsh:R Non-Histone Cell Biology Spindle apparatus NDC80 Microscopy Fluorescence Hela Cells Multiprotein Complexes biology.protein lcsh:Q Generic health relevance 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | PLoS ONE PloS one, vol 4, iss 8 PLoS ONE, Vol 4, Iss 8, p e6831 (2009) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0006831 |
| Popis: | Condensins I and II in vertebrates are essential ATP-dependent complexes necessary for chromosome condensation in mitosis. Condensins depletion is known to perturb structure and function of centromeres, however the mechanism of this functional link remains elusive. Depletion of condensin activity is now shown to result in a significant loss of loading of CENP-A, the histone H3 variant found at active centromeres and the proposed epigenetic mark of centromere identity. Absence of condensins and/or CENP-A insufficiency produced a specific kinetochore defect, such that a functional mitotic checkpoint cannot prevent chromosome missegregation resulting from improper attachment of sister kinetochores to spindle microtubules. Spindle microtubule-dependent deformation of both inner kinetochores and the HEC1/Ndc80 microtubule-capturing module, then results in kinetochore separation from the Aurora B pool and ensuing reduced kinase activity at centromeres. Moreover, recovery from mitosis-inhibition by monastrol revealed a high incidence of merotelic attachment that was nearly identical with condensin depletion, Aurora B inactivation, or both, indicating that the Aurora B dysfunction is the key defect leading to chromosome missegregation in condensin-depleted cells. Thus, beyond a requirement for global chromosome condensation, condensins play a pivotal role in centromere assembly, proper spatial positioning of microtubule-capturing modules and positioning complexes of the inner centromere versus kinetochore plates. |
| Databáze: | OpenAIRE |
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