Williams Jessica S, Hayashi Takeshi, Yanagida Mitsuhiro, Russell Paul
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 90237, USA.
Mol Cell. 2009 Feb 13;33(3):287-98. doi: 10.1016/j.molcel.2009.01.017.
Mis16 and Mis18 are subunits of a protein complex required for incorporation of the histone H3 variant CenH3 (Cnp1/CENP-A) into centromeric chromatin in Schizosaccharomyces pombe and mammals. How the Mis16-Mis18 complex performs this function is unknown. Here, we report that the Mis16-Mis18 complex is required for centromere localization of Scm3(Sp), a Cnp1-binding protein related to Saccharomyces cerevisiae Scm3. Scm3(Sp) is required for centromeric localization of Cnp1, while Scm3(Sp) localizes at centromeres independently of Cnp1. Like the Mis16-Mis18 complex but unlike Cnp1, Scm3(Sp) dissociates from centromeres during mitosis. Inactivation of Scm3(Sp) or Mis18 increases centromere localization of histones H3 and H2A/H2B, which are largely absent from centromeres in wild-type cells. Whereas S. cerevisiae Scm3 is proposed to replace histone H2A/H2B in centromeric nucleosomes, the dynamic behavior of S. pombe Scm3 suggests that it acts as a Cnp1 assembly/maintenance factor that directly mediates the stable deposition of Cnp1 into centromeric chromatin.
Mis16和Mis18是一种蛋白质复合物的亚基，该复合物是粟酒裂殖酵母和哺乳动物着丝粒染色质中组蛋白H3变体CenH3（Cnp1/CENP-A）整合所必需的。Mis16-Mis18复合物如何执行这一功能尚不清楚。在此，我们报告Mis16-Mis18复合物是Scm3（Sp）着丝粒定位所必需的，Scm3（Sp）是一种与酿酒酵母Scm3相关的Cnp1结合蛋白。Scm3（Sp）是Cnp1着丝粒定位所必需的，而Scm3（Sp）独立于Cnp1定位于着丝粒。与Mis16-Mis18复合物一样但与Cnp1不同，Scm3（Sp）在有丝分裂期间从着丝粒解离。Scm3（Sp）或Mis18的失活增加了组蛋白H3和H2A/H2B的着丝粒定位，而在野生型细胞的着丝粒中这些组蛋白基本不存在。虽然有人提出酿酒酵母Scm3在着丝粒核小体中取代组蛋白H2A/H2B，但粟酒裂殖酵母Scm3的动态行为表明它作为一种Cnp1组装/维持因子，直接介导Cnp1稳定沉积到着丝粒染色质中。
