학술논문

Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation.
Document Type
Article
Source
Nature Structural & Molecular Biology. Sep2011, Vol. 18 Issue 9, p1015-1019. 5p. 1 Black and White Photograph, 3 Graphs.
Subject
*PHOSPHORYLATION
*RECOMBINANT DNA
*SURGICAL excision
*SACCHAROMYCES cerevisiae
*DNA topoisomerases
*PHYSIOLOGY
*THERAPEUTICS
Language
ISSN
1545-9993
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 dna2?N248 mutant proteins promote resection only in the presence of Exo1, suggesting cross-talk between Dna2- and Exo1-dependent resection pathways. [ABSTRACT FROM AUTHOR]