CDK targets Sae2 to control DNA-end resection and homologous recombination.

Nature
Pablo HuertasStephen P Jackson

Abstract

DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a S...Continue Reading

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Citations

Jun 24, 2009·Cellular and Molecular Life Sciences : CMLS·Sang Eun Lee, Kyungjae Myung
Aug 11, 2010·Cellular and Molecular Life Sciences : CMLS·Feyruz V Rassool, Alan E Tomkinson
Oct 29, 2009·Chromosoma·Agnieszka RupnikMuriel Grenon
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Jul 28, 2009·Nature Structural & Molecular Biology·Emilie RassBernard S Lopez
Jan 7, 2010·Nature Structural & Molecular Biology·Pablo Huertas
Dec 7, 2010·Nature Structural & Molecular Biology·Mieun Lee-TheilenJayanta Chaudhuri
Aug 16, 2011·Nature Structural & Molecular Biology·Xuefeng ChenGrzegorz Ira
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