Contribution of base excision repair, nucleotide excision repair, and DNA recombination to alkylation resistance of the fission yeast Schizosaccharomyces pombe
Contribution of base excision repair, nucleotide excision repair, and DNA recombination to alkylation resistance of the fission yeast Schizosaccharomyces pombe
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DOI：
10.1128/jb.182.8.2104-2112.2000
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发表时间：
2000-04-01
影响因子：
3.2
通讯作者：
Samson, L
中科院分区：
文献类型：
--
作者：
Memisoglu, A;Samson, L
DNA损伤是不可避免的，整个进化谱系的生物都拥有对细胞存活和基因组稳定性至关重要的DNA修复途径。为了了解碱基切除修复(BER)在保护真核细胞免受烷化剂攻击中的作用，我们构建了Mag13-甲基腺嘌呤DNA糖基酶基因突变的庞氏裂殖酵母菌株。我们报告说，S.pombe Mag1突变体对甲基化损伤的敏感性只有轻微的增加，这表明Mag1启动的BER在该生物体的烷基化抗性中起着令人惊讶的微小作用。我们进一步证明，在烷基化抗性中，其他DNA修复途径比BER发挥更大的作用。与核苷酸切除修复(Rad13)和重组修复(Rhp51)相关的基因突变比Mag1突变体对烷基化更敏感。此外，在DNA修复中的确切功能尚不清楚的翻盖内切酶rad2基因突变株也比mag1突变株对烷基化反应更敏感。此外，Mag1和rad13在耐烷基化方面存在协同作用，并且Mag1和rhp51表现出令人惊讶的复杂的遗传相互作用。讨论了DER在烷基化诱导的S.pombe DNA链断裂中的作用模型。
DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe pombe strains mutant for the mag13-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive than mag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive than mag1 mutants. Further, mag1 and rad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of DER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.