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减数分裂 DNA 双链断裂的处理需要细胞周期蛋白依赖性激酶和多种核酸酶。

Processing of meiotic DNA double strand breaks requires cyclin-dependent kinase and multiple nucleases.

机构信息

Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.

出版信息

J Biol Chem. 2010 Apr 9;285(15):11628-37. doi: 10.1074/jbc.M110.104083. Epub 2010 Feb 11.


DOI:10.1074/jbc.M110.104083
PMID:20150422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2857040/
Abstract

Meiotic recombination requires the formation of programmed Spo11-dependent DNA double strand breaks (DSBs). In Saccharomyces cerevisiae, the Sae2 protein and the Mre11-Rad50-Xrs2 complex are necessary to remove the covalently attached Spo11 protein from the DNA ends, which are then resected by so far unknown nucleases. Here, we demonstrate that phosphorylation of Sae2 Ser-267 by cyclin-dependent kinase 1 (Cdk1) is required to initiate meiotic DSB resection by allowing Spo11 removal from DSB ends. This finding suggests that Cdk1 activity is required for the processing of Spo11-induced DSBs, thus providing a mechanism for coordinating DSB resection with progression through meiotic prophase. Furthermore, the helicase Sgs1 and the nucleases Exo1 and Dna2 participate in lengthening the 5'-3' resection tracts during meiosis by controlling a step subsequent to Spo11 removal.

摘要

减数分裂重组需要形成程序化的 Spo11 依赖性 DNA 双链断裂 (DSB)。在酿酒酵母中,Sae2 蛋白和 Mre11-Rad50-Xrs2 复合物对于从 DNA 末端去除共价连接的 Spo11 蛋白是必要的,然后由目前未知的核酸内切酶进行切除。在这里,我们证明了 cyclin-dependent kinase 1 (Cdk1) 对 Sae2 Ser-267 的磷酸化对于通过允许 Spo11 从 DSB 末端去除来启动减数分裂 DSB 切除是必需的。这一发现表明 Cdk1 活性对于 Spo11 诱导的 DSB 的处理是必需的,从而为协调 DSB 切除与减数分裂前期的进展提供了一种机制。此外,解旋酶 Sgs1 和核酸内切酶 Exo1 和 Dna2 通过控制 Spo11 去除后的一个步骤参与延长减数分裂过程中的 5'-3' 切除片段。

相似文献

[1]
Processing of meiotic DNA double strand breaks requires cyclin-dependent kinase and multiple nucleases.

J Biol Chem. 2010-2-11

[2]
Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.

Nature. 2008-10-9

[3]
CDK and Mec1/Tel1-catalyzed phosphorylation of Sae2 regulate different responses to DNA damage.

Nucleic Acids Res. 2019-12-2

[4]
Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection.

Proc Natl Acad Sci U S A. 2018-12-3

[5]
Mre11 and Exo1 contribute to the initiation and processivity of resection at meiotic double-strand breaks made independently of Spo11.

DNA Repair (Amst). 2010-12-13

[6]
Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends.

Cell. 2008-9-19

[7]
Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks.

EMBO J. 2010-9-10

[8]
Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation.

Nat Struct Mol Biol. 2011-8-14

[9]
DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2.

Nature. 2010-9-2

[10]
The 9-1-1 Complex Controls Mre11 Nuclease and Checkpoint Activation during Short-Range Resection of DNA Double-Strand Breaks.

Cell Rep. 2020-10-20

引用本文的文献

[1]
SPO-Seq: An Accessible Method for Efficient Evaluation of Spo11 Catalytic Activity and Profiling Meiotic DSB Hotspots in Saccharomyces cerevisiae.

Methods Mol Biol. 2024

[2]
Chk2 homolog Mek1 limits exonuclease 1-dependent DNA end resection during meiotic recombination in Saccharomyces cerevisiae.

Genetics. 2024-9-4

[3]
Genetic control of meiosis surveillance mechanisms in mammals.

Front Cell Dev Biol. 2023-2-23

[4]
Phospho-Regulation of Meiotic Prophase.

Front Cell Dev Biol. 2021-4-13

[5]
ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP.

Proc Natl Acad Sci U S A. 2021-3-23

[6]
CDK Regulation of Meiosis: Lessons from and .

Genes (Basel). 2020-6-29

[7]
The Arabidopsis Cdk1/Cdk2 homolog CDKA;1 controls chromosome axis assembly during plant meiosis.

EMBO J. 2020-2-3

[8]
CDK and Mec1/Tel1-catalyzed phosphorylation of Sae2 regulate different responses to DNA damage.

Nucleic Acids Res. 2019-12-2

[9]
Processing of DNA Double-Strand Breaks by the MRX Complex in a Chromatin Context.

Front Mol Biosci. 2019-6-7

[10]
Regulatory control of DNA end resection by Sae2 phosphorylation.

Nat Commun. 2018-10-1

本文引用的文献

[1]
Multiple pathways regulate 3' overhang generation at S. cerevisiae telomeres.

Mol Cell. 2009-7-10

[2]
DNA double-strand breaks in meiosis: checking their formation, processing and repair.

DNA Repair (Amst). 2009-9-2

[3]
CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle.

Nature. 2009-5-21

[4]
Human CtIP mediates cell cycle control of DNA end resection and double strand break repair.

J Biol Chem. 2009-4-3

[5]
DNA helicases Sgs1 and BLM promote DNA double-strand break resection.

Genes Dev. 2008-10-15

[6]
Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.

Nature. 2008-10-9

[7]
Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends.

Cell. 2008-9-19

[8]
CDK targets Sae2 to control DNA-end resection and homologous recombination.

Nature. 2008-10-2

[9]
Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast.

Genes Dev. 2008-2-1

[10]
Sae2 is an endonuclease that processes hairpin DNA cooperatively with the Mre11/Rad50/Xrs2 complex.

Mol Cell. 2007-11-30

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