Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter Cells.
Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter Cells.
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DOI：
10.1016/j.celrep.2017.04.055
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发表时间：
2017-05-16
期刊：
影响因子：
8.8
通讯作者：
Spencer SL
中科院分区：
文献类型：
--
作者：
Arora M;Moser J;Phadke H;Basha AA;Spencer SL
哺乳动物细胞有两种根本不同的状态-增殖和静止-但我们对细胞如何以及为什么在这些状态之间转换的理解是有限的。我们以前表明，积极增殖的人口包含一个亚群，进入静止（G 0）在一个明显的随机方式。使用CDK 2活性和DNA损伤的单细胞延时成像，我们现在表明，在以前的（母亲）细胞周期的内源性复制应力提示p21依赖性进入子细胞进入静止后立即有丝分裂。此外，子细胞处于静止状态的时间与遗传损伤的程度相关。因此，我们的研究将一个细胞周期中的复制错误与随后细胞周期中子细胞的命运联系起来。更广泛地说，这项工作揭示了进入静止状态并不是纯粹的随机性，而是具有很强的确定性成分，这些成分来自于对上一代发生的事件的记忆。Arora等人发现，母细胞中未解决的DNA复制错误传递给子细胞，促使子细胞进入暂时的静止状态，其持续时间与遗传损伤的程度相关。因此，作者揭示了细胞周期持续时间异质性的关键来源。
Mammalian cells have two fundamentally different states – proliferative and quiescent – but our understanding of how and why cells switch between these states is limited. We previously showed that actively proliferating populations contain a subpopulation that enters quiescence (G0) in an apparently stochastic manner. Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show that endogenous replication stress in the previous (mother) cell cycle prompts p21-dependent entry of daughter cells into quiescence immediately after mitosis. Furthermore, the amount of time daughter cells spend in quiescence is correlated with the extent of inherited damage. Our study thus links replication errors in one cell cycle to the fate of daughter cells in the subsequent cell cycle. More broadly, this work reveals that entry into quiescence is not purely stochastic but has a strong deterministic component arising from a memory of events that occurred in the previous generation(s). Arora et al. find that unresolved DNA replication errors in mother cells are passed on to daughter cells, prompting entry of daughter cells into a temporary quiescence whose duration is correlated with the extent of inherited damage. The authors thereby uncover a key source of heterogeneity in cell-cycle duration.
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影响因子：
9.8
作者：
Coller HA;Sang L;Roberts JM
通讯作者：
Roberts JM
影响因子：
3.5
作者：
Gelot C;Magdalou I;Lopez BS
通讯作者：
Lopez BS
影响因子：
64.5
作者：
Cappell SD;Chung M;Jaimovich A;Spencer SL;Meyer T
通讯作者：
Meyer T
DOI：
10.1083/jcb.201011083
发表时间：
2011-04-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harrigan JA;Belotserkovskaya R;Coates J;Dimitrova DS;Polo SE;Bradshaw CR;Fraser P;Jackson SP
通讯作者：
Jackson SP
DOI：
10.1073/pnas.0606343104
发表时间：
2006-12-26
影响因子：
11.1
作者：
Barboza, Juan A.;Liu, Geng;Lozano, Guillermina
通讯作者：
Lozano, Guillermina