The repair of DNA methylation damage in Saccharomyces cerevisiae
The repair of DNA methylation damage in Saccharomyces cerevisiae
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DOI：
10.1007/s002940050157
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发表时间：
1996-12
期刊：
影响因子：
2.5
通讯作者：
W. Xiao;B. L. Chow;L. Rathgeber
中科院分区：
文献类型：
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作者：
W. Xiao;B. L. Chow;L. Rathgeber
甲磺酸甲酯 (MMS) 的主要遗传毒性是由于产生致命的 3-甲基腺嘌呤 (3MeA) 损伤。酵母中的烷基化特异性碱基切除修复途径由 Mag1 3MeA DNA 糖基化酶启动，该酶去除受损的碱基，然后是 Apn1 无嘌呤/无嘧啶核酸内切酶，在脱碱基位点切割 DNA 链以进行后续修复。 MMS 也被认为是一种放射模拟剂，因为许多 DNA 辐射修复突变体也对 MMS 敏感。为了了解这些辐射修复基因如何参与 DNA 甲基化修复，我们通过将酵母 mag1 和 apn1 突变与 RAD3、RAD6 和 RAD52 组中每个组中涉及的突变相结合进行了上位分析。我们发现携带rad6、rad18、rad50和rad52单突变的细胞对MMS的杀伤比mag1突变体更敏感，双突变体比相应的单突变体更敏感，并且双突变体的作用要么是相加的要么是协同的，这表明复制后和重组修复途径要么识别与MAG1和APN1相同的损伤，要么识别MMS处理产生的一些不同损伤。通过重组和复制后修复处理的损伤不仅仅是3MeA，因为MAG1基因的过度表达并不能抵消这些途径的损失。基于上述分析，我们讨论了通过各种途径修复甲基化损伤的可能机制。
The major genotoxicity of methyl methanesulfonate (MMS) is due to the production of a lethal 3-methyladenine (3MeA) lesion. An alkylation-specific base-excision repair pathway in yeast is initiated by a Mag1 3MeA DNA glycosylase that removes the damaged base, followed by an Apn1 apurinic/ apyrimidinic endonuclease that cleaves the DNA strand at the abasic site for subsequent repair. MMS is also regarded as a radiomimetic agent, since a number of DNA radiation-repair mutants are also sensitive to MMS. To understand how these radiation-repair genes are involved in DNA methylation repair, we performed an epistatic analysis by combining yeastmag1andapn1mutations with mutations involved in each of theRAD3,RAD6andRAD52groups. We found that cells carryingrad6,rad18,rad50andrad52single mutations are far more sensitive to killing by MMS than themag1mutant, that double mutants were much more sensitive than either of the corresponding single mutants, and that the effects of the double mutants were either additive or synergistic, suggesting that post-replication and recombination-repair pathways recognize either the same lesions as MAG1 and APN1, or else some differ- ent lesions produced by MMS treatment. Lesions handled by recombination and post replication repair are not simply 3MeA, since over-expression of theMAG1gene does not offset the loss of these pathways. Based on the above analyses, we discuss possible mechanisms for the repair of methylation damage by various pathways.