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

Journal Article


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 Rum 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.

Publication Date


  • 2022

Citation


  • Ojha, D., Jaszczur, M. M., Sikand, A., McDonald, J. P., Robinson, A., Van Oijen, A. M., . . . Goodman, M. F. (2022). Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase. Nucleic Acids Research, 50(12), 6854-6869. doi:10.1093/nar/gkac515

Scopus Eid


  • 2-s2.0-85134539700

Start Page


  • 6854

End Page


  • 6869

Volume


  • 50

Issue


  • 12

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 Rum 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.

Publication Date


  • 2022

Citation


  • Ojha, D., Jaszczur, M. M., Sikand, A., McDonald, J. P., Robinson, A., Van Oijen, A. M., . . . Goodman, M. F. (2022). Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase. Nucleic Acids Research, 50(12), 6854-6869. doi:10.1093/nar/gkac515

Scopus Eid


  • 2-s2.0-85134539700

Start Page


  • 6854

End Page


  • 6869

Volume


  • 50

Issue


  • 12