Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase
Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase
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DOI：
10.1016/j.celrep.2020.107533
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发表时间：
2020-04-21
期刊：
影响因子：
8.8
通讯作者：
Hickson, Ian D.
中科院分区：
文献类型：
--
作者：
Venegas, Andres Bueno;Natsume, Toyoaki;Hickson, Ian D.
在DNA修复的背景下，已经大量研究了粘附素和缩合素相关的SMC 5/6复合物。然而，SMC 5/6即使在没有细胞应激的情况下也具有不确定的基本功能。通过使用生长素诱导的降解系统快速消耗亚基的SMC 5/6复合物，我们表明，SMC 5/6是必不可少的癌源性和正常的人类细胞的生存能力。SMC 5/6功能受损与DNA损伤、p53激活、细胞周期停滞和衰老的自发诱导以及各种有丝分裂染色体分离异常的频率增加相关。然而，我们发现，只有当SMC 5/6的功能在前面的S和G2期受损时，这种染色体的错误分离才是明显的。相比之下，降解的SMC 5/6之前立即有丝分裂进入染色体分离的保真度几乎没有或没有影响，突出的重要性，以确保忠实的姐妹染色单体分离的复合物在间期。
The cohesin- and condensin-related SMC5/6 complex has largely been studied in the context of DNA repair. Nevertheless, SMC5/6 has an undefined essential function even in the absence of cellular stress. Through the use of an auxin-inducible degradation system for rapidly depleting subunits of the SMC5/6 complex, we show that SMC5/6 is essential for viability in cancer-derived and normal human cells. Impairment of SMC5/6 function is associated with spontaneous induction of DNA damage, p53 activation, cell-cycle arrest, and senescence, as well as an increased frequency of various mitotic chromosome segregation abnormalities. However, we show that this chromosome missegregation is apparent only when SMC5/6 function is impaired during the preceding S and G2 phases. In contrast, degradation of SMC5/6 immediately prior to mitotic entry has little or no impact on the fidelity of chromosome segregation, highlighting the importance of the complex during interphase in order to ensure faithful sister chromatid disjunction.