Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase.

Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase.
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DOI:
10.1093/nar/gkac515
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发表时间:
2022-07-08
影响因子:
14.9
通讯作者:
Goodman, Myron F.
Goodman, Myron F.
中科院分区:
生物学2区
文献类型:
--
作者:
Ojha, Debika;Jaszczur, Malgorzata M.;Sikand, Adhirath;McDonald, John P.;Robinson, Andrew;van Oijen, Antoine M.;Mak, Chi H.;Pinaud, Fabien;Cox, Michael M.;Woodgate, Roger;Goodman, Myron F.

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诱变性大肠杆菌DNA聚合酶V(pol V)的同源物由许多病原体和移动的元件编码。我们使用来自整合接合元件(ICE)R391的Rum pol(鲁马′ 2 B)作为模型移动的元件编码的聚合酶(MEPol)。高度致突变的朗姆酒pol水平转移到各种受体细胞,包括许多病原体。在物种之间移动,目前还不清楚Rum pol是否可以自行发挥作用或需要宿主因子的激活。在这里,我们表明Rum pol生化活性需要形成一个物理突变体复合物Rum Mut,含有鲁马′2B-RecA-ATP,RecA由每个受体细菌捐赠。对于R391,Rum Mut的体外比活性和体内诱变率取决于宿主细胞RecA与E. coli RecA. Rum pol是一种高度保守和有效的快速进化的移动的催化剂,具有产生广泛突变景观的潜力,其可以用于确保细菌在富含抗生素的环境中的适应性,从而导致抗生素抗性的建立。
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.
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