The Dot1 Histone Methyltransferase and the Rad9 Checkpoint Adaptor Contribute to Cohesin-Dependent Double-Strand Break Repair by Sister Chromatid Recombination in Saccharomyces cerevisiae
The Dot1 Histone Methyltransferase and the Rad9 Checkpoint Adaptor Contribute to Cohesin-Dependent Double-Strand Break Repair by Sister Chromatid Recombination in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.109.101899
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发表时间：
2009-06-01
期刊：
影响因子：
3.3
通讯作者：
San-Segundo, Pedro A.
中科院分区：
文献类型：
--
作者：
Conde, Francisco;Refolio, Esther;San-Segundo, Pedro A.
基因组完整性受到多种DNA损伤来源的威胁。DNA双链断裂（DSB）是最危险的DNA损伤类型之一，可以由内源性或外源性因子产生，但它们也可以在DNA复制过程中产生。姐妹染色单体重组（SCR）是复制过程中产生的DSB修复的关键机制，是维持基因组稳定性的基础。正确的修复依赖于多种因素，其中组蛋白修饰在DSB反应中起重要作用。在此，我们研究了组蛋白H3K79甲基转移酶Dot1在复制依赖性SCR修复中的作用。HO诱导的DSB，作为评估其在同源重组中的功能的一种方式。我们表明，DOLI，Rad9 DNA损伤检查点适配器，和组蛋白H2A（γ H2A）的磷酸化是必需的有效的SCR。此外，我们发现，Dot1和Rad9促进DSB诱导的粘附素加载到染色质上。我们认为，招募Rad9 DSB网站介导的γ H2A和H3K79甲基化有助于DSB修复通过SCR调节的粘附素结合到损伤部位。因此，我们的结果有助于了解不同的染色质修饰如何影响DNA修复机制，这对于维持基因组稳定性至关重要。
Genomic integrity is threatened by multiple Sources of DNA damage. DNA double-strand breaks (DSBs) are among the most dangerous types of DNA lesions and can be generated by endogenous or exogenous agents, but they can arise also during DNA replication. Sister chromatid recombination (SCR) is a key mechanism for the repair of DSBs generated during replication and it is fundamental for maintaining genomic stability. Proper repair relies oil several factors, among which histone modifications play important roles in the response to DSBs. Here, we study the role of the histone H3K79 methyltransferase Dot1 in the repair by SCR of replication-dependent. HO-induced DSBs, as a way to assess its function in homologous recombination. We show that DOLI, the Rad9 DNA damage checkpoint adaptor, and phosphorylation of histone H2A (gamma H2A) are required for efficient SCR. Moreover, we show that Dot1 and Rad9 promote DSB-induced loading of cohesin onto chromatin. We propose that recruitment of Rad9 to DSB sites mediated by gamma H2A and H3K79 methylation contributes to DSB repair via SCR by regulating cohesin binding to damage sites. Therefore, our results contribute to all understanding of how different chromatin modifications impinge on DNA repair mechanisms, which are fundamental for maintaining genomic stability.