The yeast RSC chromatin-remodeling complex is required for kinetochore function in chromosome segregation

The yeast RSC chromatin-remodeling complex is required for kinetochore function in chromosome segregation
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DOI:
10.1128/mcb.23.9.3202-3215.2003
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发表时间:
2003-05-01
影响因子:
5.3
通讯作者:
Laurent, BC
Laurent, BC
中科院分区:
生物学2区
文献类型:
--
作者:
Hsu, JM;Huang, J;Laurent, BC

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染色体的精确分离需要动粒,这是一种复杂的蛋白质机器,它组装到着丝粒DNA上,以介导复制的姐妹染色单体附着到有丝分裂纺锤体上。这项研究揭示了一个重要的作用,酵母RSC ATP依赖的染色质重塑复合物在动粒染色体传递。编码RSC两个核心亚基的基因突变,ATP酶Sth1p和Snf5p同源物Sfh1p,与编码动粒蛋白的基因突变和着丝粒DNA突变发生遗传相互作用。RSC还与着丝粒染色质的组蛋白和组蛋白变体组分在遗传和物理上相互作用。重要的是,RSC定位于着丝粒和近着丝粒染色体区域,并且其与这些位点的关联依赖于Sth 1p。sth1和sfh1突变体都表现出改变的着丝粒和近着丝粒染色质结构和真实染色体的错误分离增加。最后,RSC是不需要的组蛋白H3变体Cse4p的着丝粒沉积,这表明RSC在重新配置着丝粒和侧翼核小体后Cse4p招聘适当的染色体传递的作用。
The accurate segregation of chromosomes requires the kinetochore, a complex protein machine that assembles onto centromeric DNA to mediate attachment of replicated sister chromatids to the mitotic spindle apparatus. This study reveals an important role for the yeast RSC ATP-dependent chromatin-remodeling complex at the kinetochore in chromosome transmission. Mutations in genes encoding two core subunits of RSC, the ATPase Sth1p and the Snf5p homolog Sfh1p, interact genetically with mutations in genes encoding kinetochore proteins and with a mutation in centromeric DNA. RSC also interacts genetically and physically with the histone and histone variant components of centromeric chromatin. Importantly, RSC is localized to centromeric and centromere-proximal chromosomal regions, and its association with these loci is dependent on Sth1p. Both sth1 and sfh1 mutants exhibit altered centromeric and centromere-proximal chromatin structure and increased missegregation of authentic chromosomes. Finally, RSC is not required for centromeric deposition of the histone H3 variant Cse4p, suggesting that RSC plays a role in reconfiguring centromeric and flanking nucleosomes following Cse4p recruitment for proper chromosome transmission.