title: Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation.
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 dna2ΔN248 mutant proteins promote resection only in the presence of Exo1, suggesting cross-talk between Dna2- and Exo1-dependent resection pathways.
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Chen
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.forename: Woo-Hyun
authors.initials: WH
authors.lastname: Chung
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Alma
authors.initials: A
authors.lastname: Papusha
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Shim
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Ira
mesh_terms: D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008957:Models, Genetic; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D004265:DNA Helicases; C410222:DNA2 protein, S cerevisiae