TitleMutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis elegans
Publication TypeJournal Article
Year of Publication2005
AuthorsDenver, DR, Feinberg, S, Estes, S, Thomas, WK, Lynch, M
JournalGenetics
Volume170
Pagination107-113
Type of ArticleJournal Article
ISSN0016-6731
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 similar to 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 similar to 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.

URL<Go to ISI>://WOS:000229677500011
DOI10.1534/genetics.104.038521