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Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2022-06-23 , DOI: 10.1093/nar/gkac515
Debika Ojha 1 , Malgorzata M Jaszczur 1 , Adhirath Sikand 2 , John P McDonald 3 , Andrew Robinson 4, 5 , Antoine M van Oijen 4, 5 , Chi H Mak 1, 2, 6 , Fabien Pinaud 1, 2, 7 , Michael M Cox 8 , Roger Woodgate 3 , Myron F Goodman 1, 2
Affiliation  

Homologs of the mutagenic Escherichia coli DNA polymerase V (pol V) are encoded by numerous pathogens and mobile elements. We have used Rum pol (RumA′2B), from the integrative conjugative element (ICE), R391, as a model mobile element-encoded polymerase (MEPol). The highly mutagenic Rum pol is transferred horizontally into a variety of recipient cells, including many pathogens. Moving between species, it is unclear if Rum pol can function on its own or requires activation by host factors. Here, we show that Rum pol biochemical activity requires the formation of a physical mutasomal complex, Rum Mut, containing RumA′2B-RecA-ATP, with RecA being donated by each recipient bacteria. For R391, Rum Mut specific activities in vitro and mutagenesis rates in vivo depend on the phylogenetic distance of host-cell RecA from E. coli RecA. Rum pol is a highly conserved and effective mobile catalyst of rapid evolution, with the potential to generate a broad mutational landscape that could serve to ensure bacterial adaptation in antibiotic-rich environments leading to the establishment of antibiotic resistance.

中文翻译:

宿主细胞 RecA 激活移动元件编码的诱变 DNA 聚合酶

诱变性大肠杆菌 DNA 聚合酶 V (pol V) 的同系物由许多病原体和移动元件编码。我们使用来自整合结合元件 (ICE) R391 的 Rum pol (RumA'2B) 作为模型移动元件编码聚合酶 (MEPol)。高度致突变的 Rum pol 被水平转移到各种受体细胞中,包括许多病原体。在物种之间移动,尚不清楚 Rum pol 是否可以自行发挥作用或需要宿主因素激活。在这里,我们表明 Rum pol 生化活性需要形成物理突变复合体 Rum Mut,其中包含 RumA'2B-RecA-ATP,每个受体细菌都提供 RecA。对于 R391,Rum Mut 的体外特异性活性和体内诱变率取决于宿主细胞 RecA 与大肠杆菌 RecA 的系统发育距离。
更新日期:2022-06-23
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