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

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.

Pubmed ID: 21841787

Authors

  • Chen X
  • Niu H
  • Chung WH
  • Zhu Z
  • Papusha A
  • Shim EY
  • Lee SE
  • Sung P
  • Ira G

Journal

Nature structural & molecular biology

Publication Data

September 6, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 3R01 GM071011
  • Agency: NIGMS NIH HHS, Id: 3R01GM080600
  • Agency: NIGMS NIH HHS, Id: GM071011
  • Agency: NIGMS NIH HHS, Id: GM080600
  • Agency: NIGMS NIH HHS, Id: R01 GM080600
  • Agency: NIGMS NIH HHS, Id: R01 GM080600-04
  • Agency: NIEHS NIH HHS, Id: R01ES07061
  • Agency: NIGMS NIH HHS, Id: R01GM57814

Mesh Terms

  • CDC2 Protein Kinase
  • DNA Breaks, Double-Stranded
  • DNA Helicases
  • Exodeoxyribonucleases
  • Intracellular Signaling Peptides and Proteins
  • Models, Genetic
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Recombination, Genetic
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins