Processing of Meiotic DNA Double Strand Breaks Requires Cyclin-dependent Kinase and Multiple Nucleases

被引:38
作者
Manfrini, Nicola [1 ]
Guerini, Ilaria [1 ]
Citterio, Andrea [1 ]
Lucchini, Giovanna [1 ]
Longhese, Maria Pia [1 ]
机构
[1] Univ Milano Bicocca, Dipartimento Biotecnol & Biosci, I-20126 Milan, Italy
关键词
BUDDING YEAST SAE2; CELL-CYCLE; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; END RESECTION; CHROMOSOME SEGREGATION; DAMAGE RESPONSE; HUMAN CTIP; MEIOSIS; REPAIR;
D O I
10.1074/jbc.M110.104083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:11628 / 11637
页数:10
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