Mismatch repair-dependent mutagenesis in nondividing cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 16; pp. 6153 - 6158
• Main Authors: Rodriguez, Gina P, Romanova, Nina V, Bao, Gaobin, Rouf, N. Cynthia, Kow, Yoke Wah, Crouse, Gray F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.04.2012; National Acad Sciences
• Subjects: Base Sequence; Biological Sciences; Cell cycle; Cell growth; Cellular biology; Deoxyribonucleic acid; DNA; DNA Damage; DNA Mismatch Repair; DNA Mismatch Repair - genetics; DNA repair; DNA Replication; DNA Replication - genetics; DNA, Fungal; DNA, Fungal - genetics; DNA, Fungal - metabolism; DNA-Binding Proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electroporation; genes; Genetic mutation; genetics; Genotype; Genotype & phenotype; Immunoglobulins; Messenger RNA; metabolism; mismatch repair; Models, Genetic; Mutagenesis; Mutation; neoplasms; Nucleotide sequence; nucleotide sequences; Nucleotides; phenotype; Replication; rev genes; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; somatic hypermutation; Tryptophan Synthase; Tryptophan Synthase - genetics; Tryptophan Synthase - metabolism; Tumors; Yeasts
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1115361109

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.