...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Expanded Substrate Scope of DNA Polymerase theta and DNA Polymerase beta:Lyase Activity on 5 '-Overhangs and Clustered Lesions
【24h】

Expanded Substrate Scope of DNA Polymerase theta and DNA Polymerase beta:Lyase Activity on 5 '-Overhangs and Clustered Lesions

机译：扩增DNA聚合酶THETA和DNA聚合酶β的底物范围：5'左右的裂解酶活性和聚集病变

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

DNA polymerase theta (Pol theta) is a multifunctional enzyme with double-strand break (DSB) repair, translesion synthesis, and lyase activities. Pol theta lyase activity on ternary substrates containing a 5'-dRP that are produced during base excision repair of abasic sites (AP) is weak compared to that of DNA polymerase beta (Pol beta), a polymerase integrally involved in base excision repair. This led us to explore whether Pol theta utilizes its lyase activity to remove 5'-dRP and incise abasic sites from alternative substrates that might be produced during DNA damage and repair. We found that Pol theta exhibited lyase activity on abasic lesions near DSB termini and on clustered lesions. To calibrate the Pol theta activity, Pol beta reactivity was examined with the same substrates. Pol beta excised 5'-dRP from within a 5'-overhang 80 times faster than did Pol theta. Pol theta and Pol beta also incised AP within clustered lesions but showed opposite preferences with respect to the polarity of the lesions. AP lesions in 5'-overhangs were typically excised by Pol beta 35-50 times faster than those in a duplex substrate but 15-20-fold more slowly than 5'-dRP in a ternary complex. This is the first report of Pol theta exhibiting lyase activity within an unincised strand. These results suggest that bifunctional polymerases may exhibit lyase activity on a greater variety of substrates than previously recognized. A role in DSB repair could potentially be beneficial, while the aberrant activity exhibited on clustered lesions may be deleterious because of their conversion to DSBs.
机译：DNA聚合酶THETA（POL THETA）是一种多官能酶，具有双链断裂（DSB）修复，翻塑合成和裂解酶活性。与DNA聚合酶β（POLβ）相比，含有5'-DRP的含有5'-DRP的三元碱基上的粘酶活性，与DNA聚合酶β（POLβ）相比，其整体参与基础切除修复的聚合酶。这导致我们探索POL THEA是否利用其裂解酶活性以从DNA损伤和修复期间可以从可能产生的替代底物中去除5'-DRP和切除脱脂位点。我们发现Pol Theta在DSB Termini附近的Abasic病变和聚类病变上表现出裂解酶活性。为了校准POLθ活动，用相同的基材检查POLβ反应性。 Pol Beta从5'-overhang内切除5'-DRP 80倍，比Polθ更快。 Pol Theta和Polβ还在聚簇病变中切开AP，但相对于病变的极性显示相反的偏好。 5'-突出的AP病变通常通过POLβ比双链衬底中的速度快35-50倍，但在三元复合物中比5'-DRP更缓慢地为15-20倍。这是Pol Theta在悬在一起在一个悬在一起的裂解酶活性的第一个报告。这些结果表明双官能聚合酶可以在比先前识别的更大的基材上表现出裂解酶活性。在DSB修复中的作用可能是有益的，而在聚类病变上表现出的异常活动可能因转换为DSB而有害。

著录项

  • 来源
    《Biochemistry》 |2018年第42期|共9页
  • 作者

    Laverty Daniel J.; Greenberg Marc M.;

  • 作者单位

    Johns Hopkins Univ Dept Chem 3400 North Charles St Baltimore MD 21218 USA;

    Johns Hopkins Univ Dept Chem 3400 North Charles St Baltimore MD 21218 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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