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 language | English (US) |
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Pages (from-to) | 1015-1019 |
Number of pages | 5 |
Journal | Nature Structural and Molecular Biology |
Volume | 18 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2011 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology