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Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase.
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.
Afiliação
  • Ojha D; Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Jaszczur MM; Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Sikand A; Department of Chemistry, University of Southern California, Los Angeles, Los Angeles, CA 90089, USA.
  • McDonald JP; Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Robinson A; Molecular Horizons Institute and School of Chemistry and Biomolecular Science, University of Wollongong, Wollongong, NSW 2522, Australia.
  • van Oijen AM; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
  • Mak CH; Molecular Horizons Institute and School of Chemistry and Biomolecular Science, University of Wollongong, Wollongong, NSW 2522, Australia.
  • Pinaud F; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
  • Cox MM; Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Woodgate R; Department of Chemistry, University of Southern California, Los Angeles, Los Angeles, CA 90089, USA.
  • Goodman MF; Center of Applied Mathematical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Nucleic Acids Res ; 50(12): 6854-6869, 2022 07 08.
Article em En | MEDLINE | ID: mdl-35736210
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Recombinases Rec A / Escherichia coli / Mutagênicos Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Recombinases Rec A / Escherichia coli / Mutagênicos Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article