title: Functional characterization of two SOS-regulated genes involved in mitomycin C resistance in Caulobacter crescentus.
abstract: The SOS response is a universal bacterial regulon involved in the cellular response to DNA damage and other forms of stress. In Caulobacter crescentus, previous work has identified a plethora of genes that are part of the SOS regulon, but the biological roles of several of them remain to be determined. In this study, we report that two genes, hereafter named mmcA and mmcB, are involved in the defense against DNA damage caused by mitomycin C (MMC), but not against lesions induced by other common DNA damaging agents, such as UVC light, methyl methanesulfonate (MMS) and hydrogen peroxide. mmcA is a conserved gene that encodes a member of the glyoxalases/dioxygenases protein family, and acts independently of known DNA repair pathways. On the other hand, epistasis analysis showed that mmcB acts in the same pathway as imuC (dnaE2), and is required specifically for MMC-induced mutagenesis, but not for that induced by UV light, suggesting a role for MmcB in translesion synthesis-dependent repair of MMC damage. We show that the lack of MMC-induced mutability in the mmcB strain is not caused by lack of proper SOS induction of the imuABC operon, involved in translesion synthesis (TLS) in C. crescentus. Based on this data and on structural analysis of a close homolog, we propose that MmcB is an endonuclease which creates substrates for ImuABC-mediated TLS patches.
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Carina O
authors.initials: CO
authors.lastname: Lopes-Kulishev
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Alves
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Estela Y
authors.initials: EY
authors.lastname: Valencia
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: María I
authors.initials: MI
authors.lastname: Pidhirnyj
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Fernández-Silva
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Ticiane R
authors.initials: TR
authors.lastname: Rodrigues
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Cristiane R
authors.initials: CR
authors.lastname: Guzzo
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: rgalhard@usp.br.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Galhardo
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D020134:Catalytic Domain; D016935:Caulobacter crescentus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D017124:Conserved Sequence; D004249:DNA Damage; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004843:Epistasis, Genetic / Q000187:drug effects / Q000528:radiation effects; D017353:Gene Deletion; D005798:Genes, Bacterial; D050296:Microbial Viability / Q000187:drug effects / Q000528:radiation effects; D016685:Mitomycin / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000528:radiation effects; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013014:SOS Response, Genetics / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D001426:Bacterial Proteins; D016685:Mitomycin
keywords: Caulobacter crescentus; Endonucleases; Mitomycin C; SOS response; Translesion synthesis; dnaE2; imuC