Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae
Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae
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DOI：
10.1016/j.dnarep.2006.12.010
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发表时间：
2007-03-01
期刊：
影响因子：
3.8
通讯作者：
Thompson, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Bostelman, Lindsey J.;Keller, Andrew M.;Thompson, Jeffrey S.
在酿酒酵母中，已经发现多种蛋白质在紫外线损伤DNA的修复和异染色质介导的沉默中起作用。特别是，参与组蛋白H3的赖氨酸-79的甲基化的因素被牵连在这两个过程中，这表明这种修饰的双向功能。我们发现，dot 1无效突变和组蛋白H3点突变在赖氨酸-79导致增加的敏感性紫外线辐射，这表明赖氨酸-79甲基化是重要的有效修复紫外线损伤。dot 1和各种UV修复基因之间的上位性分析表明，赖氨酸-79甲基化在核苷酸切除、复制后和重组修复途径以及RAD 9介导的检查点功能中发挥重叠作用。相反，上位性分析与H3赖氨酸-79点突变表明，赖氨酸到谷氨酸取代发挥特定的影响内的核苷酸切除修复和复制后修复途径，这表明该等位基因只破坏了一个子集的赖氨酸-79甲基化的功能。总体结果表明，组蛋白H3赖氨酸-79甲基化在对紫外线损伤的反应中存在独特和可分离的作用，可能有助于协调各种修复过程。(c)2007 Elsevier B. V.保留所有权利。
Various proteins have been found to play roles in both the repair of UV damaged DNA and heterochromatin-mediated silencing in the yeast Saccharomyces cerevisiae. In particular, factors that are involved in the methylation of lysine-79 of histone H3 by Dot1p have been implicated in both processes, suggesting a bipartite function for this modification. We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting that lysine-79 methylation is important for efficient repair of UV damage. Epistasis analysis between dot1 and various UV repair genes indicates that lysine-79 methylation plays overlapping roles within the nucleotide excision, post-replication and recombination repair pathways, as well as RAD9-mediated checkpoint function. In contrast, epistasis analysis with the H3 lysine-79 point mutation indicates that the lysine-to-glutamic acid substitution exerts specific effects within the nucleotide excision repair and post-replication repair pathways, suggesting that this allele only disrupts a subset of the functions of lysine-79 methylation. The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes. (c) 2007 Elsevier B.V. All rights reserved.