Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization.

Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization.
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DOI:
10.1111/j.1365-2958.2008.06336.x
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发表时间:
2008-08
影响因子:
3.6
通讯作者:
Salama NR
Salama NR
中科院分区:
生物学2区
文献类型:
--
作者:
Amundsen SK;Fero J;Hansen LM;Cromie GA;Solnick JV;Smith GR;Salama NR

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幽门螺杆菌在人胃中的定植以严重的致病性炎症为特征。细菌蛋白质解毒活性氧或识别受损的DNA加合物促进感染,这表明H。pylori需要DNA损伤修复才能在体内成功定植。修复的分子机制仍然未知。我们确定了同源的AddAB类解旋酶核酸酶,相关的大肠杆菌RecBCD酶,其中,RecA,是修复DNA断裂和同源重组所需的。H. pylori缺失addA或addB基因的突变体缺乏可检测的ATP依赖性核酸酶活性,克隆的H. pylori addAB基因恢复了E. colirecBCD缺失突变体。H. pylori addAB和recA突变体具有降低的胃定殖能力。这些突变体对DNA损伤剂敏感,并且在编码外膜蛋白的同源基因之间具有降低的表观基因转换频率。我们的研究结果揭示了在急性和慢性阶段的H。幽门螺杆菌胃感染
Helicobacter pylori colonization of the human stomach is characterized by profound disease-causing inflammation. Bacterial proteins that detoxify reactive oxygen species or recognize damaged DNA adducts promote infection, suggesting that H. pylori requires DNA damage-repair for successful in vivo colonization. The molecular mechanisms of repair remain unknown. We identified homologs of the AddAB class of helicase-nuclease enzymes, related to the Escherichia coli RecBCD enzyme, which, with RecA, is required for repair of DNA breaks and homologous recombination. H. pylori mutants lacking addA or addB genes lack detectable ATP-dependent nuclease activity, and the cloned H. pylori addAB genes restore both nuclease and helicase activities to an E. coli recBCD deletion mutant. H. pylori addAB and recA mutants have a reduced capacity for stomach colonization. These mutants are sensitive to DNA damaging agents and have reduced frequencies of apparent gene conversion between homologous genes encoding outer membrane proteins. Our results reveal requirements for double-strand break repair and recombination during both acute and chronic phases of H. pylori stomach infection.
DOI: 10.1073/pnas.83.15.5558
发表时间: 1986-08-01
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