Institute of Molecular Cancer Research, Faculty of Medicine, University of Zurich Zurich, Switzerland.
Front Genet. 2013 Jun 3;4:99. doi: 10.3389/fgene.2013.00099. eCollection 2013.
DNA double-strand breaks (DSBs) are repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR and NHEJ is highly regulated during the cell cycle. DNA-end resection, an evolutionarily conserved process that generates long stretches of single-stranded DNA, plays a critical role in pathway choice, as it commits cells to HR, while, at the same time, suppressing NHEJ. As erroneous DSB repair is a major source of genomic instability-driven tumorigenesis, DNA-end resection factors, and in particular their regulation by post-translational modifications, have become the subject of extensive research over the past few years. Recent work has implicated phosphorylation at S/T-P motifs by cyclin-dependent kinases (CDKs) as a major regulatory mechanism of DSB repair. Intriguingly, CDK activity was found to be critically important for the coordinated and timely execution of DNA-end resection, and key players in this process were subsequently identified as CDK substrates. In this mini review, we provide an overview of the current understanding of how the DNA-end resection machinery in yeast and human cells is controlled by CDK-mediated phosphorylation.
DNA 双链断裂 (DSBs) 通过两种主要途径进行修复：同源重组 (HR) 和非同源末端连接 (NHEJ)。在细胞周期中，HR 和 NHEJ 之间的选择受到高度调控。DNA 末端切除是一种进化上保守的过程，它产生长的单链 DNA 片段，在途径选择中起着关键作用，因为它促使细胞进行 HR，同时抑制 NHEJ。由于错误的 DSB 修复是导致基因组不稳定性驱动肿瘤发生的主要来源，因此 DNA 末端切除因子，特别是它们的翻译后修饰调节，已成为过去几年广泛研究的主题。最近的工作表明，细胞周期蛋白依赖性激酶 (CDKs) 对 S/T-P 基序的磷酸化是 DSB 修复的主要调节机制。有趣的是，CDK 活性对于 DNA 末端切除的协调和及时执行至关重要，随后确定该过程中的关键参与者为 CDK 底物。在这篇迷你综述中，我们概述了目前对酵母和人类细胞中 DNA 末端切除机制如何受 CDK 介导的磷酸化控制的理解。
