Department of Biochemistry, University of Oxford, Oxford, UK.
EMBO J. 2013 Mar 6;32(5):656-65. doi: 10.1038/emboj.2012.346. Epub 2013 Jan 22.
Cohesin's Smc1, Smc3, and kleisin subunits create a tripartite ring within which sister DNAs are entrapped. Evidence suggests that DNA enters through a gate created by transient dissociation of the Smc1/3 interface. Release at the onset of anaphase is triggered by proteolytic cleavage of kleisin. Less well understood is the mechanism of release at other stages of the cell cycle, in particular during prophase when most cohesin dissociates from chromosome arms in a process dependent on the regulatory subunit Wapl. We show here that Wapl-dependent release from salivary gland polytene chromosomes during interphase and from neuroblast chromosome arms during prophase is blocked by translational fusion of Smc3's C-terminus to kleisin's N-terminus. Our findings imply that proteolysis-independent release of cohesin from chromatin is mediated by Wapl-dependent escape of DNAs through a gate created by transient dissociation of the Smc3/kleisin interface. Thus, cohesin's DNA entry and exit gates are distinct.
着丝粒蛋白的 Smc1、Smc3 和 kleisin 亚基在其中形成一个三聚体环，姐妹 DNA 被捕获在这个环内。有证据表明，DNA 通过 Smc1/3 界面短暂解离形成的门进入。在有丝分裂前期，kleisin 的蛋白水解切割触发了释放。在细胞周期的其他阶段（特别是在前期），当大多数着丝粒蛋白在依赖于调节亚基 Wapl 的过程中从染色体臂上解离时，其释放的机制理解得较少。我们在这里表明，唾液腺多线染色体在间期和神经母细胞染色体臂在前期与 kleisin 的 N 端融合的 Smc3 的 C 端的翻译融合，阻断了 Wapl 依赖性释放。我们的发现意味着，染色质中依赖于蛋白水解的黏连蛋白的释放是由 Wapl 依赖性通过 Smc3/kleisin 界面的短暂解离形成的门的 DNA 逃逸介导的。因此，黏连蛋白的 DNA 进入和退出门是不同的。
