The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast.
The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast.
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DOI：
10.1093/nar/gkx240
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发表时间：
2017-06-20
影响因子：
14.9
通讯作者：
Wysocki R
中科院分区：
文献类型：
--
作者：
Litwin I;Bakowski T;Maciaszczyk-Dziubinska E;Wysocki R
准确的染色体分离对于每个活细胞都是必不可少的，因为细胞分裂期间染色体的不均匀分布可能导致基因组不稳定性，这在致癌和发育障碍中表现出来。Irc5是酿酒酵母中保守的Snf2家族的一员，其功能尚不清楚。在这里，我们确定Irc5作为一个新的相互作用的cohesin复杂。Irc5与Scc1 cohesin亚基结合，并有助于cohesin与染色质结合。IRC5的破坏降低了着丝粒和染色体臂的粘着蛋白水平，导致过早的姐妹染色单体分离。此外，在缺乏IRC5的细胞中，rDNA区域的粘附素占据减少导致rDNA重复序列的丢失。我们还表明，Irc5的移位酶活性是其在凝聚力途径中的功能所必需的。最后，我们证明，在没有Irc5的情况下，染色质结合Scc2的水平，一个成员的粘附素加载复合物，和Scc1和Scc2之间的物理相互作用减少。我们的研究结果表明，Irc5是一个辅助因子，参与了粘着蛋白与染色质的关联。
Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin.