Structural basis for Scc3-dependent cohesin recruitment to chromatin.
Structural basis for Scc3-dependent cohesin recruitment to chromatin.
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DOI：
10.7554/elife.38356
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发表时间：
2018-08-15
期刊：
影响因子：
7.7
通讯作者：
Panne D
中科院分区：
文献类型：
--
作者：
Li Y;Muir KW;Bowler MW;Metz J;Haering CH;Panne D
粘附素环复合体是许多染色体交易所必需的，包括姐妹染色单体凝聚、DNA损伤修复和转录调控。粘附素如何与染色质底物接合仍然是一个悬而未决的问题。在这里，我们通过确定与Scc1 kleisin亚基和DNA片段结合的发芽酵母粘附素热重复亚基Scc3的晶体结构，表明Scc3和Scc1形成了一个复合的DNA相互作用模块。Scc3-Scc1亚复合体通过一个保守的、带正电的表面与双链DNA结合。我们证明，这个保守的结构域对于Scc3-Scc1在体外与DNA结合是必需的，也是在染色体上浓缩粘附素和细胞存活所必需的。这些发现表明，Scc3-Scc1 DNA结合界面在粘附素复合体募集到染色体上并因此使粘附素在细胞分裂过程中忠实地执行其功能方面发挥着核心作用。
The cohesin ring complex is required for numerous chromosomal transactions including sister chromatid cohesion, DNA damage repair and transcriptional regulation. How cohesin engages its chromatin substrate has remained an unresolved question. We show here, by determining a crystal structure of the budding yeast cohesin HEAT-repeat subunit Scc3 bound to a fragment of the Scc1 kleisin subunit and DNA, that Scc3 and Scc1 form a composite DNA interaction module. The Scc3-Scc1 subcomplex engages double-stranded DNA through a conserved, positively charged surface. We demonstrate that this conserved domain is required for DNA binding by Scc3-Scc1 in vitro, as well as for the enrichment of cohesin on chromosomes and for cell viability. These findings suggest that the Scc3-Scc1 DNA-binding interface plays a central role in the recruitment of cohesin complexes to chromosomes and therefore for cohesin to faithfully execute its functions during cell division.