Specialized interfaces of Smc5/6 control hinge stability and DNA association.
Specialized interfaces of Smc5/6 control hinge stability and DNA association.
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DOI：
10.1038/ncomms14011
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发表时间：
2017-01-30
影响因子：
16.6
通讯作者：
Oliver AW
中科院分区：
文献类型：
--
作者：
Alt A;Dang HQ;Wells OS;Polo LM;Smith MA;McGregor GA;Welte T;Lehmann AR;Pearl LH;Murray JM;Oliver AW
染色体结构维持 (SMC) 复合体：粘连蛋白、凝缩蛋白和 Smc5/6 参与高阶染色体结构的组织，这对于染色体的精确复制和分离至关重要。每个复合物均由特定的 SMC 蛋白二聚体（真核生物中的异二聚体）支撑，通过铰链域连接在一起。在这里，我们表明，Smc5/6-铰链与粘连蛋白和凝缩蛋白的铰链一样，也形成环形结构，但具有其他 SMC 复合物所不存在的独特亚基界面；一个不寻常的“分子锁”和一个功能性的“中心”。这些界面中的特定突变会导致严重的表型效应，导致裂殖酵母对 DNA 损伤剂敏感，并降低人类细胞的活力。我们表明，Smc5/6 铰链复合物优先与 ssDNA 结合，并且这种相互作用受到“latch”和“hub”突变的影响，表明这些独特特征在 Smc5/6 复合物控制 DNA 关联方面发挥着关键作用。染色体结构维护 (SMC) 复合物通过调节染色体分离来维持基因组完整性。在这里，Alt 等人。描述了裂殖酵母异二聚体 Smc5/6-铰链的结构，并定义了对 Smc5/6 细胞功能至关重要的功能特征。
The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure—which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual ‘molecular latch' and a functional ‘hub'. Defined mutations in these interfaces cause severe phenotypic effects with sensitivity to DNA-damaging agents in fission yeast and reduced viability in human cells. We show that the Smc5/6-hinge complex binds preferentially to ssDNA and that this interaction is affected by both ‘latch' and ‘hub' mutations, suggesting a key role for these unique features in controlling DNA association by the Smc5/6 complex. Structural Maintenance of Chromosomes (SMC) complexes maintain genome integrity by regulating the segregation of chromosomes. Here, Alt et al. describe the structure of the heterodimeric Smc5/6-hinge from fission yeast and define functional features critical for Smc5/6's cellular function.