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PMID: 21841787 Published · epublish English Journal Article Research Support, N.I.H., Extramural

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

Nature structural & molecular biology ·Vol. 18 ·No. 9 ·2011-08-14 ·Pages 1015-9

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

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.

MeSH Terms
CDC2 Protein Kinase/chemistry,physiology DNA Breaks, Double-Stranded DNA Helicases/metabolism Exodeoxyribonucleases/metabolism Intracellular Signaling Peptides and Proteins/metabolism Models, Genetic Phosphorylation Protein Serine-Threonine Kinases/metabolism Recombination, Genetic Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism,physiology
Chemicals
Intracellular Signaling Peptides and Proteins Saccharomyces cerevisiae Proteins MEC1 protein, S cerevisiae Protein Serine-Threonine Kinases CDC2 Protein Kinase Exodeoxyribonucleases exodeoxyribonuclease I DNA Helicases DNA2 protein, S cerevisiae
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chen Xuefeng
Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Niu Hengyao
Chung Woo-Hyun
Zhu Zhu
Papusha Alma
Shim Eun Yong
Lee Sang Eun
Sung Patrick
Ira Grzegorz
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2105
Published
2011-08-14
Epub
2011-00-14
Pages
1015-9
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3168961
Subset
IM
Grants
NIGMS NIH HHS · R01GM57814 · United States
NIGMS NIH HHS · R01 GM080600-04 · United States
NIEHS NIH HHS · R01ES07061 · United States
NIGMS NIH HHS · 3R01 GM071011 · United States
NIGMS NIH HHS · R01 GM057814 · United States
NIGMS NIH HHS · R01 GM080600 · United States
NIEHS NIH HHS · R01 ES007061 · United States
NIGMS NIH HHS · GM080600 · United States
NIGMS NIH HHS · R01 GM071011 · United States
NIGMS NIH HHS · 3R01GM080600 · United States
NIGMS NIH HHS · GM071011 · United States
External Links
PubMed source DOI: 10.1038/nsmb.2105 PMC Full Text View journal details
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