Title: Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation.

Authors: Chen, Xuefeng; Niu, Hengyao; Chung, Woo-Hyun; Zhu, Zhu; Papusha, Alma; Shim, Eun Yong; Lee, Sang Eun; Sung, Patrick; Ira, Grzegorz

Published In Nat Struct Mol Biol, (2011 Sep)

Abstract: DNA recombination pathways are regulated by the cell cycle to coordinate with replication. Cyclin-dependent kinase (Cdk1) promotes efficient 5' strand resection at DNA double-strand breaks (DSBs), the initial step of homologous recombination and damage checkpoint activation. The Mre11-Rad50-Xrs2 complex with Sae2 initiates resection, whereas two nucleases, Exo1 and Dna2, and the DNA helicase-topoisomerase complex Sgs1-Top3-Rmi1 generate longer ssDNA at DSBs. Using Saccharomyces cerevisiae, we provide evidence for Cdk1-dependent phosphorylation of the resection nuclease Dna2 at Thr4, Ser17 and Ser237 that stimulates its recruitment to DSBs, resection and subsequent Mec1-dependent phosphorylation. Poorly recruited dna2T4A S17A S237A and dna2ýýN248 mutant proteins promote resection only in the presence of Exo1, suggesting cross-talk between Dna2- and Exo1-dependent resection pathways.

PubMed ID: 21841787

MeSH Terms: CDC2 Protein Kinase/chemistry; CDC2 Protein Kinase/physiology*; DNA Breaks, Double-Stranded*; DNA Helicases/metabolism*; Exodeoxyribonucleases/metabolism; Intracellular Signaling Peptides and Proteins/metabolism; Models, Genetic; Phosphorylation; Protein-Serine-Threonine Kinases/metabolism; Recombination, Genetic; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae Proteins/physiology*; Saccharomyces cerevisiae/genetics*; Saccharomyces cerevisiae/metabolism