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H2A.Z-Dependent Regulation of Cohesin Dynamics on Chromosome Arms

机译:H2A.Z依赖染色体细胞粘附素动力学的调节。

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Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are major determinants of chromosome structure and dynamics. The cohesin complex embraces sister chromatids throughout interphase, but during mitosis most cohesin is stripped from chromosome arms by early prophase, while the remaining cohesin at kinetochores is cleaved at anaphase. This two-step removal of cohesin is required for sister chromatids to separate. The cohesin-related Smc5/6 complex has been studied mostly as a determinant of DNA repair via homologous recombination. However, chromosome segregation fails in Smc5/6 null mutants or cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs in the fission yeast Schizosaccharomyces pombe following genotoxic and replication stress, or topoisomerase II dysfunction, and these mitotic defects are due to the postanaphase retention of cohesin on chromosome arms. Here we show that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe. Further, we identified the histone variant H2A.Z as a critical factor to modulate cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome integrity through accurate chromosome segregation.
机译:染色体(SMC)复合物和DNA拓扑异构酶的结构维持是染色体结构和动力学的主要决定因素。粘着蛋白复合物在整个相间都包含姐妹染色单体,但是在有丝分裂期间,大多数粘着蛋白会在早期前期从染色体臂上剥离,而其余的粘着蛋白则在后期分裂。姐妹染色单体分离需要粘附分子的两步去除。粘着蛋白相关的Smc5 / 6复合体已被广泛研究为通过同源重组修复DNA的决定因素。但是,染色体分离在Smc5 / 6无效突变体或小干扰RNA处理的细胞中失败。这也发生在遗传毒性和复制压力或拓扑异构酶II功能异常后的裂变酵母裂殖酵母裂殖酵母Smc5 / 6亚型中,这些有丝分裂缺陷归因于黏附蛋白在染色体臂后的后期保留。在这里,我们显示Smc5 / 6的有丝分裂和修复作用在粟酒裂殖酵母中在基因上是可分离的。此外,我们确定组蛋白变体H2A.Z是调节黏附素动力学的关键因素,缺乏H2A.Z的细胞可抑制Smc5 / 6功能障碍所致的有丝分裂缺陷。 H2A.Z和SMC复合物一起可通过准确的染色体分离确保基因组完整性。

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