A bacterial DNA repair pathway specific to a natural antibiotic

Abstract

SummaryAll organisms possess several DNA repair pathways to maintain the integrity of their genetic material. Although there are several DNA repair pathways that are well understood, we recently identified several genes in Bacillus subtilis that are important for surviving treatment with drugs that damage DNA. Here, we report a drug specific DNA repair pathway in B. subtilis. We identified genes coding for a previously uncharacterized helicase and exonuclease, mrfA and mrfB, respectively. Deletion of mrfA and mrfB resulted in sensitivity to the DNA damaging agent mitomycin C, but not other types of DNA damage. We found that MrfAB operate independently of canonical nucleotide excision repair, forming a novel excision repair pathway in bacteria. A phylogenetic analysis demonstrates that MrfAB homologs are present in diverse bacterial phyla, and a cross-complementation assay shows that MrfAB function is conserved in closely related species. Mitomycin C is a natural antibiotic that is produced by the soil dwelling bacterium Streptomyces lavendulae, and B. subtilis is also a soil dwelling organism. The specificity of the ΔmrfAB phenotype suggests that MrfAB have been adapted as a countermeasure to mitomycin producing bacteria.Abbreviated SummaryBacteria possess DNA repair pathways to maintain the integrity of their genetic material. The helicase MrfA and the exonuclease MrfB are part of a mitomycin C specific DNA repair pathway in Bacillus subtilis. Despite being present in many bacterial species, MrfAB activity in repairing MMC damaged DNA appears to be restricted to closely related species, suggesting that these proteins have likely been adapted to the specific needs of each bacterium.