A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion
A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion
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DOI：
10.1091/mbc.e17-08-0511
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发表时间：
2018-02-01
影响因子：
3.3
通讯作者：
Koshland, Douglas
中科院分区：
文献类型：
--
作者：
Robison, Brett;Guacci, Vincent;Koshland, Douglas
粘附素是姐妹染色单体凝聚、染色体凝聚、DNA损伤修复和转录调控所必需的保守蛋白质复合体。虽然粘附素具有连接DNA双链的功能，但它的各个结构域对这一活动的贡献仍然知之甚少。我们用随机插入突变的方法对粘附素的Smc3p亚基进行了询问。对Smc3p铰链上的一个突变体的分析表明，该结构域在凝聚力维持和凝聚方面发挥了意想不到的作用。进一步的研究发现，Smc3p的铰链在粘附素稳定结合到染色体之后的一步发挥作用，并且不受Eco1p乙酰转移酶的调节。铰链突变表型类似于Pds5p的丢失，Pds5p与Smc3p头区附近的铰链相对结合。我们认为Smc3p铰链和Pds5p的特定构象相互作用，促进凝聚力的维持和凝聚。
Cohesin is a conserved protein complex required for sister chromatid cohesion, chromosome condensation, DNA damage repair, and regulation of transcription. Although cohesin functions to tether DNA duplexes, the contribution of its individual domains to this activity remains poorly understood. We interrogated the Smc3p subunit of cohesin by random insertion mutagenesis. Analysis of a mutant in the Smc3p hinge revealed an unexpected role for this domain in cohesion maintenance and condensation. Further investigation revealed that the Smc3p hinge functions at a step following cohesin's stable binding to chromosomes and independently of Smc3p's regulation by the Eco1p acetyltransferase. Hinge mutant phenotypes resemble loss of Pds5p, which binds opposite the hinge near Smc3p's head domain. We propose that a specific conformation of the Smc3p hinge and Pds5p cooperate to promote cohesion maintenance and condensation.