title: Error-prone processing of apurinic/apyrimidinic (AP) sites by PolX underlies a novel mechanism that promotes adaptive mutagenesis in Bacillus subtilis.
abstract: In growing cells, apurinic/apyrimidinic (AP) sites generated spontaneously or resulting from the enzymatic elimination of oxidized bases must be processed by AP endonucleases before they compromise cell integrity. Here, we investigated how AP sites and the processing of these noncoding lesions by the AP endonucleases Nfo, ExoA, and Nth contribute to the production of mutations (hisC952, metB5, and leuC427) in starved cells of the Bacillus subtilis YB955 strain. Interestingly, cells from this strain that were deficient for Nfo, ExoA, and Nth accumulated a greater amount of AP sites in the stationary phase than during exponential growth. Moreover, under growth-limiting conditions, the triple nfo exoA nth knockout strain significantly increased the amounts of adaptive his, met, and leu revertants produced by the B. subtilis YB955 parental strain. Of note, the number of stationary-phase-associated reversions in the his, met, and leu alleles produced by the nfo exoA nth strain was significantly decreased following disruption of polX. In contrast, during growth, the reversion rates in the three alleles tested were significantly increased in cells of the nfo exoA nth knockout strain deficient for polymerase X (PolX). Therefore, we postulate that adaptive mutations in B. subtilis can be generated through a novel mechanism mediated by error-prone processing of AP sites accumulated in the stationary phase by the PolX DNA polymerase.
authors.affiliation: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico.
authors.forename: Rocío del Carmen
authors.initials: Rdel C
authors.lastname: Barajas-Ornelas
authors.affiliation: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico.
authors.forename: Fernando H
authors.initials: FH
authors.lastname: Ramírez-Guadiana
authors.affiliation: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Juárez-Godínez
authors.affiliation: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Ayala-García
authors.affiliation: School of Life Sciences, University of Nevada, Las Vegas, Nevada, USA.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Robleto
authors.affiliation: College of Arts and Sciences, University of Missouri-St. Louis, St. Louis, Missouri, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Yasbin
authors.affiliation: Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato, Mexico pedrama@ugto.mx.
authors.forename: Mario
authors.initials: M
authors.lastname: Pedraza-Reyes
mesh_terms: D000220:Adaptation, Biological; D001412:Bacillus subtilis / Q000235:genetics* / Q000254:growth & development*; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D009154:Mutation
chemical_list: C109534:DNA polymerase X; D004259:DNA-Directed DNA Polymerase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D045643:DNA Repair Enzymes