Host cell RecA activates a mobile element-encoded mutagenic DNA polymerase-Reference-Cited by-同舟云学术

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

Published:2022-06-23 Issue:12 Volume:50 Page:6854-6869
ISSN:0305-1048
Container-title:Nucleic Acids Research
language:en
Short-container-title:

Author:

Ojha Debika¹,Jaszczur Malgorzata M¹,Sikand Adhirath²,McDonald John P³^ORCID,Robinson Andrew⁴⁵^ORCID,van Oijen Antoine M⁴⁵,Mak Chi H¹²⁶,Pinaud Fabien¹²⁷,Cox Michael M⁸^ORCID,Woodgate Roger³^ORCID,Goodman Myron F¹²^ORCID

Affiliation:

1. Department of Biological Sciences, University of Southern California , Los Angeles , CA 90089, USA

2. Department of Chemistry, University of Southern California , Los Angeles , Los Angeles , CA 90089, USA

3. Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health , Bethesda , MD 20892 , USA

4. Molecular Horizons Institute and School of Chemistry and Biomolecular Science, University of Wollongong , Wollongong, NSW 2522 , Australia

5. Illawarra Health and Medical Research Institute , Wollongong, NSW 2522 , Australia

6. Center of Applied Mathematical Sciences, University of Southern California , Los Angeles , CA 90089, USA

7. Department of Physics and Astronomy, University of Southern California , Los Angeles , CA 90089, USA

8. Department of Biochemistry, University of Wisconsin-Madison , Madison , WI 53706 Wisconsin, USA

Abstract

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.

Funder

National Institute of Environmental Health Sciences

National Institutes of General Medical Sciences

National Institutes of Child Health and Human Development, National Institutes of Health

National Institute of Neurological Disorders and Stroke

National Institutes of Health

National Science Foundation

Publisher

Oxford University Press (OUP)

Subject

Genetics

Link