Hsu Jing-Mei, Huang Jian, Meluh Pamela B, Laurent Brehon C
Department of Microbiology and Immunology, Morse Institute of Molecular Biology and Genetics, and Program in Molecular and Cellular Biology, State University of New York, Brooklyn, New York 11203, USA.
Mol Cell Biol. 2003 May;23(9):3202-15. doi: 10.1128/MCB.23.9.3202-3215.2003.
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.
染色体的精确分离需要动粒,这是一种复杂的蛋白质机器,它组装在着丝粒DNA上,介导复制后的姐妹染色单体与有丝分裂纺锤体装置的附着。这项研究揭示了酵母RSC ATP依赖的染色质重塑复合体在动粒处对染色体传递的重要作用。编码RSC两个核心亚基的基因突变,即ATP酶Sth1p和Snf5p同源物Sfh1p,与编码动粒蛋白的基因突变以及着丝粒DNA突变存在遗传相互作用。RSC还与着丝粒染色质的组蛋白和组蛋白变体成分存在遗传和物理相互作用。重要的是,RSC定位于着丝粒和着丝粒近端的染色体区域,其与这些位点的关联依赖于Sth1p。sth1和sfh1突变体均表现出着丝粒和着丝粒近端染色质结构改变,以及真实染色体错分离增加。最后,组蛋白H3变体Cse4p着丝粒沉积不需要RSC,这表明RSC在Cse4p募集后重新配置着丝粒和侧翼核小体以实现正确染色体传递中发挥作用。