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Front Genet. 2013 Jun 3;4:99. doi: 10.3389/fgene.2013.00099. eCollection 2013.

Controlling DNA-end resection: a new task for CDKs.

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1
Institute of Molecular Cancer Research, Faculty of Medicine, University of Zurich Zurich, Switzerland.

Abstract

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.

KEYWORDS:

CtIP/Sae2; DNA double-strand break repair; DNA-end resection; PIN1; cyclin-dependent kinase; homologous recombination; phosphorylation

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