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Title: A bacterial DNA repair pathway specific to a natural antibiotic
Summary

All organisms possess DNA repair pathways that are used to maintain the integrity of their genetic material. Although many DNA repair pathways are well understood, new pathways continue to be discovered. Here, we report an antibiotic specific DNA repair pathway inBacillus subtilisthat is composed of a previously uncharacterized helicase (mrfA) and exonuclease (mrfB). Deletion ofmrfAandmrfBresults in sensitivity to the DNA damaging agent mitomycin C, but not to any other type of DNA damage tested. We show that MrfAB function independent of canonical nucleotide excision repair, forming a novel excision repair pathway. We demonstrate that MrfB is a metal‐dependent exonuclease and that the N‐terminus of MrfB is required for interaction with MrfA. We determined that MrfAB failed to unhook interstrand cross‐linksin vivo, suggesting that MrfAB are specific to the monoadduct or the intrastrand cross‐link. A phylogenetic analysis uncovered MrfAB homologs in diverse bacterial phyla, and cross‐complementation indicates that MrfAB function is conserved in closely related species.B. subtilisis a soil dwelling organism and mitomycin C is a natural antibiotic produced by the soil bacteriumStreptomyces lavendulae. The specificity of MrfAB suggests that these proteins are an adaptation to environments with mitomycin producing bacteria.

 
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NSF-PAR ID:
10462513
Author(s) / Creator(s):
 ;  
Publisher / Repository:
Wiley-Blackwell
Date Published:
Journal Name:
Molecular Microbiology
Volume:
111
Issue:
2
ISSN:
0950-382X
Format(s):
Medium: X Size: p. 338-353
Size(s):
p. 338-353
Sponsoring Org:
National Science Foundation
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