title: Mismatch repair-dependent mutagenesis in nondividing cells.
abstract: Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.
authors.affiliation: Department of Biology, Department of Radiation Oncology, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Gina P
authors.initials: GP
authors.lastname: Rodriguez
authors.forename: Nina V
authors.initials: NV
authors.lastname: Romanova
authors.forename: Gaobin
authors.initials: G
authors.lastname: Bao
authors.forename: N Cynthia
authors.initials: NC
authors.lastname: Rouf
authors.forename: Yoke Wah
authors.initials: YW
authors.lastname: Kow
authors.forename: Gray F
authors.initials: GF
authors.lastname: Crouse
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D053843:DNA Mismatch Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014367:Tryptophan Synthase / Q000235:genetics / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C098790:MSH6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014367:Tryptophan Synthase