title: Roles of endonuclease V, uracil-DNA glycosylase, and mismatch repair in Bacillus subtilis DNA base-deamination-induced mutagenesis.
abstract: The disruption of ung, the unique uracil-DNA-glycosylase-encoding gene in Bacillus subtilis, slightly increased the spontaneous mutation frequency to rifampin resistance (Rif(r)), suggesting that additional repair pathways counteract the mutagenic effects of uracil in this microorganism. An alternative excision repair pathway is involved in this process, as the loss of YwqL, a putative endonuclease V homolog, significantly increased the mutation frequency of the ung null mutant, suggesting that Ung and YwqL both reduce the mutagenic effects of base deamination. Consistent with this notion, sodium bisulfite (SB) increased the Rif(r) mutation frequency of the single ung and double ung ywqL strains, and the absence of Ung and/or YwqL decreased the ability of B. subtilis to eliminate uracil from DNA. Interestingly, the Rif(r) mutation frequency of single ung and mutSL (mismatch repair [MMR] system) mutants was dramatically increased in a ung knockout strain that was also deficient in MutSL, suggesting that the MMR pathway also counteracts the mutagenic effects of uracil. Since the mutation frequency of the ung mutSL strain was significantly increased by SB, in addition to Ung, the mutagenic effects promoted by base deamination in growing B. subtilis cells are prevented not only by YwqL but also by MMR. Importantly, in nondividing cells of B. subtilis, the accumulations of mutations in three chromosomal alleles were significantly diminished following the disruption of ung and ywqL. Thus, under conditions of nutritional stress, the processing of deaminated bases in B. subtilis may normally occur in an error-prone manner to promote adaptive mutagenesis.
authors: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, México.
authors: Karina
authors: K
authors: López-Olmos
authors: Martha P
authors: MP
authors: Hernández
authors: Jorge A
authors: JA
authors: Contreras-Garduño
authors: Eduardo A
authors: EA
authors: Robleto
authors: Peter
authors: P
authors: Setlow
authors: Ronald E
authors: RE
authors: Yasbin
authors: Mario
authors: M
authors: Pedraza-Reyes
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D053843:DNA Mismatch Repair / Q000502:physiology*; D004269:DNA, Bacterial / Q000378:metabolism*; D003641:Deamination; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016296:Mutagenesis; D009154:Mutation; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D014498:Uracil; D043224:Deoxyribonuclease (Pyrimidine Dimer); D051981:Uracil-DNA Glycosidase