OVEREXPRESSION OF RNASE-H PARTIALLY COMPLEMENTS THE GROWTH DEFECT OF AN ESCHERICHIA-COLI DELTA-TOPA MUTANT - R-LOOP FORMATION IS A MAJOR PROBLEM IN THE ABSENCE OF DNA TOPOISOMERASE-I

OVEREXPRESSION OF RNASE-H PARTIALLY COMPLEMENTS THE GROWTH DEFECT OF AN ESCHERICHIA-COLI DELTA-TOPA MUTANT - R-LOOP FORMATION IS A MAJOR PROBLEM IN THE ABSENCE OF DNA TOPOISOMERASE-I
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DOI:
10.1073/pnas.92.8.3526
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发表时间:
1995-04-11
影响因子:
11.1
通讯作者:
CROUCH, RJ
CROUCH, RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DROLET, M;PHOENIX, P;CROUCH, RJ

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以前的生化研究表明,细菌DNA拓扑异构酶(TOPO)I在抑制转录过程中的R-环形成的作用,在这份报告中,我们提出了一些遗传证据,以支持一个模型,其中R-环的形成是动态调节在转录过程中的多个DNA TOPO和RNase H的活动。此外,我们的研究结果表明,在缺乏DNA TOPO I的情况下导致严重生长问题的事件与R环形成有关。我们发现,RNase H(一种降解R环RNA部分的酶)的过表达可以部分补偿DNA TOPO I的缺失。我们还注意到,DNA促旋酶的缺陷可以纠正与rnhA基因突变相关的几种表型,rnhA基因编码主要的RNA酶H活性。此外,我们发现topA和rnhA突变的组合是致命的。
Previous biochemical studies have suggested a role for bacterial DNA topoisomerase (TOPO) I in the suppression of R-loop formation during transcription, In this report, we present several pieces of genetic evidence to support a model in which R-loop formation is dynamically regulated during transcription by activities of multiple DNA TOPOs and RNase H. In addition, our results suggest that events leading to the serious growth problems in the absence of DNA TOPO I are linked to R-loop formation. We show that the overexpression of RNase H, an enzyme that degrades the RNA moiety of an R loop, can partially compensate for the absence of DNA TOPO I. We also note that a defect in DNA gyrase can correct several phenotypes associated with a mutation in the rnhA gene, which encodes the major RNase H activity. In addition, we found that a combination of topA and rnhA mutations is lethal.