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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.

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。

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