The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress
The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress
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DOI：
10.1038/ncb3343
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发表时间：
2016-05-01
影响因子：
21.3
通讯作者：
Mendoza, Manuel
中科院分区：
文献类型：
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作者：
Amaral, Nuno;Vendrell, Alexandre;Mendoza, Manuel
如果在胞质分裂完成之前未正确解决，后期染色质桥可能导致染色体断裂。 NoCut 检查点依赖于纺锤体中区的 Aurora B，可响应酵母和动物细胞中染色体分离缺陷而延迟脱落。如何检测染色质桥，以及脱落抑制是否可以防止其损伤，仍然是未解决的关键问题。我们发现由 DNA 复制应激和缩合或串联缺陷诱导的桥，但不是双着丝粒染色体，以依赖于 NoCut 的方式延迟脱落。串联和缩合缺陷导致胞质分裂期间纺锤体稳定，从而允许 Aurora B 进行桥检测。NoCut 不能防止缩合蛋白或拓扑异构酶 II 失活后的 DNA 损伤；然而，它可以保护后期桥并促进复制应激后的细胞活力。因此，染色质桥的分子起源对于NoCut的激活至关重要，而NoCut在复制应激后维持基因组稳定性方面发挥着关键作用。
Anaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.