RRC ID 35238
著者 George AA, Walworth NC.
タイトル Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe.
ジャーナル Genetics
Abstract Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis. Genetic analysis implicates a histone deacetylase (HDAC)-linked pathway in suppression because HDAC mutants clr6-1, clr3∆, and sir2∆, though not hos2∆, also promote normal mitosis in the dis1-288 mutant. Suppression of the dis phenotype through loss of msc1 function requires the spindle checkpoint protein Mad2 and is limited by the presence of the heterochromatin-associated HP1 protein homolog Swi6. We speculate that alterations in histone acetylation promote a centromeric chromatin environment that compensates for compromised dis1 function by allowing for successful kinetochore-microtubule interactions that can satisfy the SAC. In cells arrested in mitosis by mutation of dis1, loss of function of epigenetic determinants such as Msc1 or specific HDACs can promote cell survival. Because the KDM5 family of proteins has been implicated in human cancers, an appreciation of the potential role of this family of proteins in chromosome segregation is warranted.
巻・号 201(4)
ページ 1467-78
公開日 2015-12-1
DOI 10.1534/genetics.115.181792
PII genetics.115.181792
PMID 26510788
PMC PMC4676536
MeSH Centromere* Chromatin / physiology* DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology Epigenesis, Genetic* Histone Deacetylases / genetics Histone Deacetylases / metabolism Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / physiology Microtubules / physiology* Mitosis* Mutation Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / physiology
IF 4.015
引用数 5
WOS 分野 GENETICS & HEREDITY
リソース情報
酵母 FY17702 FY8617