Controlling DNA-end resection: a new task for CDKs

• Published in: Frontiers in genetics Vol. 4; p. 99
• Main Authors: Ferretti, Lorenza P., Lafranchi, Lorenzo, Sartori, Alessandro A.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2013
• Subjects: cyclin-dependent kinase; DNA double-strand break repair; DNA-end resection; Homologous Recombination; Oncology; Phosphorylation; Pin1; DNA double-strand break repair; homologous recombination; PIN1; DNA-end resection; CtIP/Sae2; cyclin-dependent kinase; phosphorylation
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2013.00099

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.