IDENTIFICATION OF CSE4-INTERACTING PROTEINS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在每个细胞周期中，染色体必须准确地分割到子细胞，以防止基因组不稳定和非整倍体，这是所有肿瘤和许多出生缺陷的标志。染色体使用着丝点进行分离，着丝点是一种特殊的蛋白质结构，组装在着丝粒DNA序列上，并中介附着到纺锤体上。所有真核着丝点的标志之一是一个重要的着丝粒的组蛋白H3(CenH3)变异体，它专门定位于着丝粒，并取代着丝粒核小体中的典型的组蛋白H3。由于着丝粒DNA序列不保守，CenH3被认为是决定着丝粒组装位置的表观遗传学成分。虽然CenH3是所有着丝点的重要组成部分，也是着丝粒染色质结构所必需的，但对CenH3掺入着丝粒DNA的情况知之甚少。因此，我们建议对发芽酵母CenH3、Cse4进行纯化，以确定可能调节其在着丝粒独占沉积的相互作用蛋白。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During every cell cycle, chromosomes must be accurately partitioned to daughter cells to prevent genomic instability and aneuploidy, a hallmark of all tumors and many birth defects. Chromosomes segregate using their kinetochores, the specialized protein structures that are assembled on centromeric DNA sequences and mediate attachment to the spindle. One hallmark of all eukaryotic kinetochores is an essential centromeric histone H3 (CenH3) variant that localizes exclusively to centromeres and replaces canonical histone H3 in centromeric nucleosomes. Because centromeric DNA sequences are not conserved, CenH3 has been proposed to be the epigenetic component that specifies the site of kinetochore assembly. Although CenH3 is an essential component of all kinetochores and is required for centromeric chromatin structure, little is known about CenH3 incorporation into centromeric DNA. We therefore propose to purify the budding yeast CenH3, Cse4, to identify interacting proteins that may regulate its exclusive deposition at the centromere.