The RAD6/BRE1 histone modification pathway in saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18
The RAD6/BRE1 histone modification pathway in saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18
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DOI：
10.1534/genetics.106.057794
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发表时间：
2006-08-01
期刊：
影响因子：
3.3
通讯作者：
Brown, J. Martin
中科院分区：
文献类型：
--
作者：
Game, John C.;Williamson, Marsha S.;Brown, J. Martin
我们研究了几个影响组蛋白H2 B和H3翻译后修饰的酵母突变体的电离辐射(IR)敏感性和上位性关系。组蛋白H2B赖氨酸123泛素化缺陷的突变体Bre1 Delta、Ige1 Delta和rtf1 Delta对IR的敏感性与我们早先报道的dot1 Delta突变体的IR敏感性相当，这与已发表的Dot1p需要H2B K123泛素化才能完全甲基化组蛋白H3 K79的发现一致。这意味着IR抵抗中的K79甲基化而不是单甲基化。H3K36甲基化缺陷的Set2 Delta突变体表现出轻微的IR敏感性，而取消H3K4甲基化的突变体类似于野生型。突变体dot1 Delta、Bre1 Delta和lge1 Delta对IR的敏感性表现为上位性。据报道，paf1 Delta突变体在H2B K123泛素化过程中也存在缺陷，没有表现出敏感性。Rad6 Delta、rad51 Null、Rad50 Delta和rad9 Delta突变与Bre1 Delta和dot1 Delta呈上位效应，而rad18 Delta和rad5 Delta与Bre1 Delta、dot1 Delta呈加性关系。Bre1 Delta rad18 Delta双突变体在敏感性上与rad6 Delta相似；因此，Rad6p在泛化H2B方面的作用解释了其比rad18 Delta更敏感的原因。我们得出结论，Bre1和DOT1诱导的IR抗性是通过同源重组修复而不是复制后修复来介导的，并证实了RAD6/Bre1/DOT1途径具有G(1)检查点作用的发现。
We examine ionizing radiation (IR) sensitivity and epistasis relationships of several Saccharomyces mutants affecting post-translational modifications of histones H2B and H3. Mutants bre1 Delta, Ige1 Delta, and rtf1 Delta, defective in histone H2B lysine 123 ubiquitination, show IR sensitivity equivalent to that of the dot1 Delta mutant that we reported on earlier, consistent with published findings that Dot1p requires H2B K123 ubiquitination to fully methylate histone H3 K79. This implicates progressive K79 methylation rather than mono-methylation in IR resistance. The set2 Delta mutant, defective in H3 K36 methylation, shows mild IR sensitivity whereas mutants that abolish H3 K4 methylation resemble wild type. The dot1 Delta, bre1 Delta, and lge1 Delta mutants show epistasis for IR sensitivity. The paf1 Delta mutant, also reportedly defective in H2B K123 ubiquitination, confers no sensitivity. The rad6 Delta, rad51null, rad50 Delta, and rad9 Delta mutations are epistatic to bre1 Delta and dot1 Delta, but rad18 Delta and rad5 Delta show additivity with bre1 Delta, dot1 Delta, and each other. The bre1 Delta rad18 Delta double mutant resembles rad6 Delta in sensitivity; thus the role of Rad6p in ubiquitinating H2B accounts for its extra sensitivity compared to rad18 Delta. We conclude that IR resistance conferred by BRE1 and DOT1 is mediated through homologous recombinational repair, not postreplication repair, and confirm findings of a G(1) checkpoint role for the RAD6/BRE1/DOT1 pathway.