Sharp Judith A, Krawitz Denise C, Gardner Kelly A, Fox Catherine A, Kaufman Paul D
Lawrence Berkeley National Laboratory and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Genes Dev. 2003 Oct 1;17(19):2356-61. doi: 10.1101/gad.1131103. Epub 2003 Sep 15.
In fission yeast and multicellular organisms, centromere-proximal regions of chromosomes are heterochromatic, containing proteins that silence gene expression. In contrast, the relationship between heterochromatin proteins and kinetochore function in the budding yeast Saccharomyces cerevisiae remains largely unexplored. Here we report that the yeast heterochromatin protein Sir1 is a component of centromeric chromatin and contributes to mitotic chromosome stability. Sir1 recruitment to centromeres occurred through a novel mechanism independent of its interaction with the origin recognition complex (ORC). Sir1 function at centromeres was distinct from its role in forming heterochromatin, because the Sir2-4 proteins were not associated with centromeric regions. Sir1 bound to Cac1, a subunit of chromatin assembly factor I (CAF-I), and helped to retain Cac1 at centromeric loci. These studies reveal that although budding yeast and mammalian cells use fundamentally different mechanisms of forming heterochromatin, they both use silencing proteins to attract the histone deposition factor CAF-I to centromeric chromatin.
在裂殖酵母和多细胞生物中，染色体着丝粒近端区域是异染色质的，含有使基因表达沉默的蛋白质。相比之下，在芽殖酵母酿酒酵母中，异染色质蛋白与动粒功能之间的关系在很大程度上仍未得到探索。在此我们报告，酵母异染色质蛋白Sir1是着丝粒染色质的一个组分，并有助于有丝分裂染色体的稳定性。Sir1募集到着丝粒是通过一种独立于其与起源识别复合物（ORC）相互作用的新机制发生的。Sir1在着丝粒处的功能与其在形成异染色质中的作用不同，因为Sir2 - 4蛋白不与着丝粒区域相关联。Sir1与染色质组装因子I（CAF - I）的一个亚基Cac1结合，并有助于将Cac1保留在着丝粒位点。这些研究表明，尽管芽殖酵母和哺乳动物细胞形成异染色质的机制根本不同，但它们都利用沉默蛋白将组蛋白沉积因子CAF - I吸引到着丝粒染色质上。
