...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Dnmt3a-CD Is Less Susceptible to Bulky Benzo[a]pyrene Diol Epoxide-Derived DNA Lesions Than Prokaryotic DNA Methyltransferases
【24h】

Dnmt3a-CD Is Less Susceptible to Bulky Benzo[a]pyrene Diol Epoxide-Derived DNA Lesions Than Prokaryotic DNA Methyltransferases

机译：与原核DNA甲基转移酶相比，Dnmt3a-CD对大体积的苯并[a] Di二酚环氧化物衍生的DNA病变的敏感性较低。

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

Benzo[a]pyrene (B[a]P) is a well-characterized environmental polycyclic aromatic hydrocarbonnpollutant. In living organisms, B[a]P is metabolized to the genotoxic anti-benzo[a]pyrene diol epoxide that reactsnwith cellular DNA to form stereoisomeric anti-B[a]PDE-N2n-dG adducts. In this study, we explored the effects ofnadduct stereochemistry and position in double-stranded DNA substrates on the functional characteristics of thencatalytic domain of murine de novo DNA methyltransferase Dnmt3a (Dnmt3a-CD). A number of 18-mernduplexes containing site-specifically incorporated (þ)- and (-)-trans-anti-B[a]PDE-N2n-dG lesions located 30n-andn50n-adjacent to and opposite the target cytosine residue were prepared. Dnmt3a-CD binds cooperatively to thenDNA duplexes with an up to 5-fold greater affinity compared to that for the undamaged DNA duplexes.nMethylation assays showed a 1.7-6.3-fold decrease in the methylation reaction rates for the damaged duplexes.nB[a]PDE modifications stimulated a nonproductive binding and markedly favored substrate inhibition ofnDnmt3a-CD in a manner independent of DNA methylation status. The latter effect was sensitive to the positionnand stereochemistry of the B[a]PDE-N2n-dGadducts. The overall effect of trans-anti-B[a]PDE-N2n-dG adducts onnDnmt3a-CD was less detrimental than in the case of the prokaryotic methyltransferases we previouslyninvestigated
机译：苯并[a] py（B [a] P）是一种特性良好的环境多环芳烃污染物。在活生物体中，B [a] P被代谢成具有遗传毒性的抗苯并[a] py二醇环氧化合物，该环氧化合物与细胞DNA反应形成立体异构的抗B [a] PDE-N2n-dG加合物。在这项研究中，我们探索了双链DNA底物的立构体立体化学和位置对鼠从头DNA甲基转移酶Dnmt3a（Dnmt3a-CD）的催化结构域功能特性的影响。制备了许多18-双链体双链体，其包含与靶胞嘧啶残基相邻且相对的30n-和n50n-位点特异性掺入的（β）-和（-）-反式-B [a] PDE-N2n-dG损伤。 Dnmt3a-CD与DNA双链体协同结合，其亲和力是未受损DNA双链体的5倍。nMethylation分析显示，受损双链体的甲基化反应速率降低了1.7-6.3倍。nB[a] PDE修饰以与DNA甲基化状态无关的方式刺激nDnmt3a-CD的非生产性结合并显着促进底物抑制。后一种效应对B [a] PDE-N2n-dGadducts的位置和立体化学敏感。反式B [a] PDE-N2n-dG加合物对nDnmt3a-CD的总体作用比我们先前研究的原核甲基转移酶的危害要小。

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