Bostelman Lindsey J, Keller Andrew M, Albrecht Ashley M, Arat Arzu, Thompson Jeffrey S
Department of Biology, Denison University, 213 Talbot Hall, Granville, Ohio 43023, USA.
DNA Repair (Amst). 2007 Mar 1;6(3):383-95. doi: 10.1016/j.dnarep.2006.12.010. Epub 2007 Jan 30.
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.
人们发现多种蛋白质在酿酒酵母中紫外线损伤DNA的修复以及异染色质介导的基因沉默过程中都发挥作用。特别地，由Dot1p介导的组蛋白H3赖氨酸-79甲基化所涉及的因子在这两个过程中都有牵连，这表明这种修饰具有双重功能。我们发现dot1基因敲除突变以及赖氨酸-79处的组蛋白H3点突变会导致对紫外线辐射的敏感性增加，这表明赖氨酸-79甲基化对于紫外线损伤的有效修复很重要。dot1与各种紫外线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RAD9介导的检查点功能中发挥重叠作用。相比之下，与H3赖氨酸-79点突变的上位性分析表明，赖氨酸到谷氨酸的取代在核苷酸切除修复和复制后修复途径中发挥特定作用，这表明该等位基因仅破坏赖氨酸-79甲基化功能的一个子集。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不同且可分离的作用，可能有助于协调各种修复过程。
