• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The 3′→5′ Exonuclease of Apn1 Provides an Alternative Pathway To Repair 7,8-Dihydro-8-Oxodeoxyguanosine in Saccharomyces cerevisiae
【24h】

The 3′→5′ Exonuclease of Apn1 Provides an Alternative Pathway To Repair 7,8-Dihydro-8-Oxodeoxyguanosine in Saccharomyces cerevisiae

机译：Apn1的3'→5'核酸外切酶为酿酒酵母中7,8-Dihydro-8-Oxodeoxyguanosine的修复提供了另一种途径

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The 8-oxo-7,8-dihydrodeoxyguanosine (8oxoG), a major mutagenic DNA lesion, results either from direct oxidation of guanines or misincorporation of 8oxodGTP by DNA polymerases. At present, little is known about the mechanisms preventing the mutagenic action of 8oxodGTP in Saccharomyces cerevisiae. Herein, we report for the first time the identification of an alternative repair pathway for 8oxoG residues initiated by S. cerevisiae AP endonuclease Apn1, which is endowed with a robust progressive 3′→5′ exonuclease activity towards duplex DNA. We show that yeast cell extracts, as well as purified Apn1, excise misincorporated 8oxoG, providing a damage-cleansing function to DNA synthesis. Consistent with these results, deletion of both OGG1 encoding 8oxoG-DNA glycosylase and APN1 causes nearly 46-fold synergistic increase in the spontaneous mutation rate, and this enhanced mutagenesis is primarily due to G · C to T · A transversions. Expression of the bacterial 8oxodGTP triphosphotase MutT in the apn1Δ ogg1Δ mutant reduces the mutagenesis. Taken together, our results indicate that Apn1 is involved in an S. cerevisiae 8-oxoguanine-DNA glycosylase (Ogg1)-independent repair pathway for 8oxoG residues. Interestingly, the human major AP endonuclease, Ape1, also exhibits similar exonuclease activity towards 8oxoG residues, raising the possibility that this enzyme could participate in the prevention of mutations that would otherwise result from the incorporation of 8oxodGTP.
机译：主要的诱变性DNA损伤是8-oxo-7,8-dihydrodeoxyguanosine（8oxoG），其是鸟嘌呤直接氧化或DNA聚合酶误掺入8oxodGTP的结果。目前，关于阻止8oxodGTP对酿酒酵母的诱变作用的机制了解甚少。在此，我们首次报告了由 S启动的8oxoG残基的替代修复途径的鉴定。酿酒酵母AP核酸内切酶Apn1，具有强大的针对双链体DNA的3'→5'核酸外切酶活性。我们表明，酵母细胞提取物，以及纯化的Apn1，消费税错误纳入8oxoG，为DNA合成提供损害清除功能。与这些结果一致，编码8oxoG-DNA糖基化酶的 OGG1 和 APN1 的缺失均导致自发突变率增加近46倍的协同增效，而这种增强的诱变主要是由于从G·C到T·A的转换。细菌8oxodGTP三磷酸酶MutT在apn1Δogg1Δ突变体中的表达减少了诱变。两者合计，我们的结果表明Apn1参与了 S。的8-氧代鸟嘌呤-DNA糖基化酶（Ogg1）的8oxoG残基独立修复途径。有趣的是，人类主要的AP核酸内切酶Ape1对8oxoG残基也显示出类似的核酸外切酶活性，从而增加了该酶可能参与预防因掺入8oxodGTP而引起的突变的可能性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号