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.

Processing of meiotic DNA double strand breaks requires cyclin-dependent kinase and multiple nucleases / N. Manfrini, I. Guerini, A. Citterio, G. Lucchini, M.P. Longhese. - In: JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 1083-351X. - 285:15(2010), pp. 11628-11637. [10.1074/jbc.M110.104083]

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

Manfrini N.;
2010

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.
Cell Cycle; Cyclin-Dependent Kinases; DNA Helicases; DNA Topoisomerases, Type II; Endodeoxyribonucleases; Endonucleases; Exodeoxyribonucleases; Phosphorylation; RecQ Helicases; Recombination, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; DNA Breaks, Double-Stranded; DNA Damage; Meiosis
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/18 - Genetica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/861046
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