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doi:10.1534/genetics.104.038521
A more recent version of this article appeared on May 1, 2005.
REGULAR RESEARCH PAPERS |
Mutation rates, spectra, and hotspots in mismatch repair-deficient Caenorhabditis elegans
Dee R Denver 1*, Seth Feinberg 1, Suzanne Estes 2, W. Kelley Thomas 3 and Michael Lynch 1
1 Indiana University
2 Oregon State University
3 University of New Hampshire
* To whom correspondence should be addressed. E-mail: ddenver{at}bio.indiana.edu.
Submitted on November 12, 2004
Revised on December 20, 2004
Accepted on 10 January 2005
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, though 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.
Key Words: Caenorhabditis elegans, Genome, Homopolymer, Mismatch Repair, Mutation
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