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

doi:10.1038/nsmb.2105

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 journal › Article › peer-review

122 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 language	English (US)
Pages (from-to)	1015-1019
Number of pages	5
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	9
DOIs	https://doi.org/10.1038/nsmb.2105
State	Published - Sep 2011

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. / Chen, Xuefeng; Niu, Hengyao; Chung, Woo Hyun; Zhu, Zhu; Papusha, Alma; Shim, Eun Yong ; Lee, Sang Eun ; Sung, Patrick; Ira, Grzegorz.

In: Nature Structural and Molecular Biology, Vol. 18, No. 9, 09.2011, p. 1015-1019.

Research output: Contribution to journal › Article › peer-review

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

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.",

author = "Xuefeng Chen and Hengyao Niu and Chung, {Woo Hyun} and Zhu Zhu and Alma Papusha and Shim, {Eun Yong} and Lee, {Sang Eun} and Patrick Sung and Grzegorz Ira",

note = "Funding Information: We thank N. Lyons and D. Morgan (University of California, San Francisco) for providing Cdk1 kinase and valuable advice. This work was supported by US National Institutes of Health (NIH) grants GM080600 and 3R01GM080600 to G.I., RO1GM57814 and RO1ES07061 to P.S., and GM071011 and 3R01 GM071011 to S.E.L.",

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AU - Lee, Sang Eun

AU - Sung, Patrick

AU - Ira, Grzegorz

N1 - Funding Information: We thank N. Lyons and D. Morgan (University of California, San Francisco) for providing Cdk1 kinase and valuable advice. This work was supported by US National Institutes of Health (NIH) grants GM080600 and 3R01GM080600 to G.I., RO1GM57814 and RO1ES07061 to P.S., and GM071011 and 3R01 GM071011 to S.E.L.

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N2 - 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.

AB - 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.

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

Abstract

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