着丝粒染色质的结构完整性和忠实的染色体分离需要 Pat1。
Structural integrity of centromeric chromatin and faithful chromosome segregation requires Pat1.
机构信息
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
出版信息
Genetics. 2013 Oct;195(2):369-79. doi: 10.1534/genetics.113.155291. Epub 2013 Jul 26.
The kinetochore (centromeric DNA and associated protein complex) is essential for faithful chromosome segregation and maintenance of genome stability. Here we report that an evolutionarily conserved protein Pat1 is a structural component of Saccharomyces cerevisiae kinetochore and associates with centromeres in a NDC10-dependent manner. Consistent with a role for Pat1 in kinetochore structure and function, a deletion of PAT1 results in delay in sister chromatid separation, errors in chromosome segregation, and defects in structural integrity of centromeric chromatin. Pat1 is involved in topological regulation of minichromosomes as altered patterns of DNA supercoiling were observed in pat1Δ cells. Studies with pat1 alleles uncovered an evolutionarily conserved region within the central domain of Pat1 that is required for its association with centromeres, sister chromatid separation, and faithful chromosome segregation. Taken together, our data have uncovered a novel role for Pat1 in maintaining the structural integrity of centromeric chromatin to facilitate faithful chromosome segregation and proper kinetochore function.
着丝粒（着丝粒 DNA 和相关蛋白复合物）对于忠实的染色体分离和基因组稳定性的维持至关重要。在这里，我们报告说，一种进化上保守的蛋白质 Pat1 是酿酒酵母着丝粒的结构组成部分，并以 NDC10 依赖性的方式与着丝粒结合。与 Pat1 在着丝粒结构和功能中的作用一致，PAT1 的缺失导致姐妹染色单体分离延迟、染色体分离错误以及着丝粒染色质结构完整性缺陷。Pat1 参与了小型染色体的拓扑调控，因为在 pat1Δ 细胞中观察到 DNA 超螺旋模式的改变。对 pat1 等位基因的研究揭示了 Pat1 中心结构域内的一个进化上保守区域，该区域对于其与着丝粒、姐妹染色单体分离和忠实染色体分离的关联是必需的。总之，我们的数据揭示了 Pat1 在维持着丝粒染色质结构完整性以促进忠实染色体分离和适当的着丝粒功能方面的新作用。
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