Shenzhen University General Hospital, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen, Guangdong, China.
Union Shenzhen Hospital, Department of Dermatology, Huazhong University of Science and Technology (Nanshan Hospital), Shenzhen, Guangdong, China.
Crit Rev Biochem Mol Biol. 2022 Jun;57(3):333-350. doi: 10.1080/10409238.2022.2027336. Epub 2022 Feb 3.
Cohesin, a four-subunit ring comprising SMC1, SMC3, RAD21 and SA1/2, tethers sister chromatids by DNA replication-coupled cohesion (RC-cohesion) to guarantee correct chromosome segregation during cell proliferation. Postreplicative cohesion, also called damage-induced cohesion (DI-cohesion), is an emerging critical player in DNA damage response (DDR). In this review, we sum up recent progress on how cohesin regulates the DNA damage checkpoint activation and repair pathway choice, emphasizing postreplicative cohesin loading and DI-cohesion establishment in yeasts and mammals. DI-cohesion and RC-cohesion show distinct features in many aspects. DI-cohesion near or far from the break sites might undergo different regulations and execute different tasks in DDR and DSB repair. Furthermore, some open questions in this field and the significance of this new scenario to our understanding of genome stability maintenance and cohesinopathies are discussed.
着丝粒由包含 SMC1、SMC3、RAD21 和 SA1/2 的四聚体环组成,通过与 DNA 复制偶联的黏合(RC 黏合)将姐妹染色单体连接起来,以保证细胞增殖过程中染色体的正确分离。复制后黏合,也称为损伤诱导黏合(DI 黏合),是 DNA 损伤反应(DDR)中的一个新兴关键因子。在这篇综述中,我们总结了近年来关于着丝粒如何调节 DNA 损伤检查点激活和修复途径选择的研究进展,重点介绍了酵母和哺乳动物中复制后黏合蛋白加载和 DI 黏合的建立。DI 黏合和 RC 黏合在许多方面具有不同的特征。靠近或远离断裂部位的 DI 黏合可能在 DDR 和 DSB 修复中受到不同的调控,并执行不同的任务。此外,还讨论了该领域的一些悬而未决的问题,以及这种新情景对我们理解基因组稳定性维持和着丝粒病的意义。