Behind the wheel and under the hood: functions of cyclin-dependent kinases in response to DNA damage.
Behind the wheel and under the hood: functions of cyclin-dependent kinases in response to DNA damage.
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DOI：
10.1016/j.dnarep.2009.04.009
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发表时间：
2009-09-02
期刊：
影响因子：
3.8
通讯作者：
Fisher RP
中科院分区：
文献类型：
--
作者：
Wohlbold L;Fisher RP
在真核生物中，细胞分裂和对遗传毒性应激的反应密切相关，例如，通过检查点途径，该途径发出DNA损伤的存在或其对细胞周期机制的持续修复的信号，导致可逆的停滞或凋亡。最近的研究揭示了另一种联系：控制DNA合成（S）期和有丝分裂的细胞周期蛋白依赖性激酶（CDK）直接协调DNA修复过程与细胞周期的进展。在哺乳动物细胞和酵母中，双链断裂（DSB）修复的两种主要模式-同源重组（HR）和非同源末端连接（NHEJ）-在细胞周期中受到调控。在酵母中，细胞周期激酶Cdk 1在G2期通过HR直接促进DSB修复。在哺乳动物细胞中，Cdk 2（在整个S和G2期具有活性的CDK）的缺失导致缺陷的DNA损伤修复和检查点信号传导。在这里，我们提供了一个概述的数据，牵连CDKs在酵母和后生动物的DNA损伤反应的调节。在酵母中，CDK活性需要在多个点的HR途径; CDK在哺乳动物HR的确切作用尚未确定。最后，我们考虑如何两个不同的，在某些情况下，相反的，CDKs的作用-作为检查点信号的负调控的目标和作为修复途径选择和功能的积极效应物-可以平衡，以产生协调和有效的响应DNA损伤。
Cell division and the response to genotoxic stress are intimately connected in eukaryotes, for example, by checkpoint pathways that signal the presence of DNA damage or its ongoing repair to the cell cycle machinery, leading to reversible arrest or apoptosis. Recent studies reveal another connection: the cyclin-dependent kinases (CDKs) that govern both DNA synthesis (S) phase and mitosis directly coordinate DNA repair processes with progression through the cell cycle. In both mammalian cells and yeast, the two major modes of double strand break (DSB) repair–homologous recombination (HR) and non-homologous end joining (NHEJ)–are reciprocally regulated during the cell cycle. In yeast, the cell cycle kinase Cdk1 directly promotes DSB repair by HR during the G2 phase. In mammalian cells, loss of Cdk2, the CDK active throughout S and G2 phases, results in defective DNA damage repair and checkpoint signaling. Here we provide an overview of data that implicate CDKs in the regulation of DNA damage responses in yeast and metazoans. In yeast, CDK activity is required at multiple points in the HR pathway; the precise roles of CDKs in mammalian HR have yet to be determined. Finally, we consider how the two different, and in some cases opposing, roles of CDKs—as targets of negative regulation by checkpoint signaling and as positive effectors of repair pathway selection and function—could be balanced to produce a coordinated and effective response to DNA damage.
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影响因子：
11.4
作者：
Aylon, Y;Liefshitz, B;Kupiec, M
通讯作者：
Kupiec, M
DOI：
10.1084/jem.20020851
发表时间：
2002-08-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Nussenzweig A
影响因子：
16
作者：
Frank, Christopher J.;Hyde, Molly;Greider, Carol W.
通讯作者：
Greider, Carol W.
影响因子：
10.5
作者：
Ferreira, MG;Cooper, JP
通讯作者：
Cooper, JP
影响因子：
10.5
作者：
EPSTEIN, CB;CROSS, FR
通讯作者：
CROSS, FR