title: Mutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis elegans.
abstract: Although it is clear that postreplicative DNA mismatch repair (MMR) plays a critical role in maintaining genomic stability in nearly all forms of life surveyed, much remains to be understood about the genome-wide impact of MMR on spontaneous mutation processes and the extent to which MMR-deficient mutation patterns vary among species. We analyzed spontaneous mutation processes across multiple genomic regions using two sets of mismatch repair-deficient (msh-2 and msh-6) Caenorhabditis elegans mutation-accumulation (MA) lines and compared our observations to mutation spectra in a set of wild-type (WT), repair-proficient C. elegans MA lines. Across most sequences surveyed in the MMR-deficient MA lines, mutation rates were approximately 100-fold higher than rates in the WT MA lines, although homopolymeric nucleotide-run (HP) loci composed of A:T base pairs mutated at an approximately 500-fold greater rate. In contrast to yeast and humans where mutation spectra vary substantially with respect to different specific MMR-deficient genotypes, mutation rates and patterns were overall highly similar between the msh-2 and msh-6 C. elegans MA lines. This, along with the apparent absence of a Saccharomyces cerevisiae MSH3 ortholog in the C. elegans genome, suggests that C. elegans MMR surveillance is carried out by a single Msh-2/Msh-6 heterodimer.
authors.affiliation: Department of Biology, Indiana University, Bloomington, 47405, USA. ddenver@bio.indiana.edu
authors.forename: Dee R
authors.initials: DR
authors.lastname: Denver
authors.forename: Seth
authors.initials: S
authors.lastname: Feinberg
authors.forename: Suzanne
authors.initials: S
authors.lastname: Estes
authors.forename: W Kelley
authors.initials: WK
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D009154:Mutation
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C450145:msh-2 protein, C elegans; C510643:msh-6 protein, C elegans; D051719:MutS DNA Mismatch-Binding Protein
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