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

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

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

DNA recombination pathways are regulated by the cell cycle to coordinate with replication. Cyclin-dependent kinase (Cdk1) promotes efficient 5-2 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 dna2 T4A S17A S237A and dna2δN248 mutant proteins promote resection only in the presence of Exo1, suggesting cross-talk between Dna2-and Exo1-dependent resection pathways.

Original languageEnglish (US)
Pages (from-to)1015-1019
Number of pages5
JournalNature Structural and Molecular Biology
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2011

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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