IDENTIFICATION OF CSE4-INTERACTING PROTEINS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在每个细胞周期中，染色体必须准确地分配给子细胞，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。 染色体利用它们的动粒分离，动粒是组装在着丝粒DNA序列上并介导与纺锤体连接的专门蛋白质结构。 所有真核动粒的一个标志是一个必需的着丝粒组蛋白H3（CenH 3）变体，其仅定位于着丝粒并取代着丝粒核小体中的典型组蛋白H3。 由于着丝粒DNA序列是不保守的，CenH 3已被提议为指定动粒组装位点的表观遗传组分。 尽管CenH 3是所有着丝粒的重要组成部分，并且是着丝粒染色质结构所必需的，但关于CenH 3掺入着丝粒DNA的情况知之甚少。 因此，我们建议纯化芽殖酵母CenH 3，Cse 4，以确定相互作用的蛋白质，可能会调节其在着丝粒的独家沉积。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.