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Originally published as Genetics Published Articles Ahead of Print on February 16, 2005.

Genetics, Vol. 170, 107-113, May 2005, Copyright © 2005
doi:10.1534/genetics.104.038521

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Mutation Rates, Spectra and Hotspots in Mismatch Repair-Deficient Caenorhabditis elegans

Dee R. Denver*,1, Seth Feinberg*, Suzanne Estes{dagger}, W. Kelley Thomas{ddagger} and Michael Lynch*

* Department of Biology, Indiana University, Bloomington, Indiana 47405
{dagger} Department of Zoology, Oregon State University, Corvallis, Oregon 97331
{ddagger} Hubbard Center for Genome Studies, University of New Hampshire, Durham, New Hampshire 03824

1 Corresponding author: Department of Biology, Indiana University, 1001 East Third St., Bloomington, IN 47405.
E-mail: ddenver{at}bio.indiana.edu

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 ~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 ~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.




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