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Chromatin dynamics mediated by histone modifiers and histone chaperones in postreplicative recombination

机译:组蛋白修饰剂和组蛋白伴侣在复制后重组中介导的染色质动力学

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摘要

Eukaryotic chromatin is regulated by chromatin factors such as histone modification enzymes, chromatin remodeling complexes and histone chaperones in a variety of DNA-dependent reactions. Among these reactions, transcription in the chromatin context is well studied. On the other hand, how other DNA-dependent reactions, including postreplicative homologous recombination, are regulated in the chromatin context remains elusive. Here, histone H3 Lys56 acetylation, mediated by the histone acetyltransferase Rtt109 and the histone chaperone Cia1/Asf1, is shown to be required for postreplicative sister chromatid recombination. This recombination did not occur in the cia1/asf1-V94R mutant, which lacks histone binding and histone chaperone activities and which cannot promote the histone acetyltransferase activity of Rtt109. A defect in another histone chaperone, CAF-1, led to an increase in acetylated H3-K56 (H3-K56-Ac)-dependent postreplicative recombination. Some DNA lesions recognized by the putative ubiquitin ligase complex Rtt101-Mms1-Mms22, which is reported to act downstream of the H3-K56-Ac signaling pathway, seem to be increased in CAF-1 defective cells. Taken together, these data provide the framework for a postreplicative recombination mechanism controlled by histone modifiers and histone chaperones in multiple ways.
机译:真核染色质在各种依赖于DNA的反应中受染色质因子(例如组蛋白修饰酶,染色质重塑复合物和组蛋白伴侣)的调节。在这些反应中,对染色质环境中的转录进行了很好的研究。另一方面,如何在染色质环境中调节其他依赖DNA的反应,包括复制后的同源重组,仍然难以捉摸。在这里,由组蛋白乙酰转移酶Rtt109和组蛋白伴侣Cia1 / Asf1介导的组蛋白H3 Lys56乙酰化被证明是复制后姐妹染色单体重组所必需的。此重组未在cia1 / asf1-V94R突变体中发生,该突变体缺乏组蛋白结合和组蛋白伴侣活性,并且不能促进Rtt109的组蛋白乙酰转移酶活性。另一个组蛋白伴侣CAF-1的缺陷导致乙酰化H3-K56(H3-K56-Ac)依赖性复制后重组的增加。据报道,假定的泛素连接酶复合物Rtt101-Mms1-Mms22识别的一些DNA损伤在CAF-1缺陷细胞中似乎增加了,据报道其作用于H3-K56-Ac信号通路的下游。总之,这些数据提供了由组蛋白修饰剂和组蛋白伴侣以多种方式控制的复制后重组机制的框架。

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