Originally published as Genetics Published Articles Ahead of Print on June 18, 2006.

Genetics, Vol. 174, 57-65, September 2006, Copyright © 2006
doi:10.1534/genetics.106.059840

The Relative Roles of Three DNA Repair Pathways in Preventing Caenorhabditis elegans Mutation Accumulation

Dee R. Denver1, Seth Feinberg, Catherine Steding, Matthew Durbin and Michael Lynch

Department of Biology, Indiana University, Bloomington, Indiana 47405

1 Corresponding author: Department of Zoology, Oregon State University, 2000 Cordley Hall, Corvallis, OR 97331-7303.
E-mail: denver{at}cgrb.oregonstate.edu

Mutation is a central biological process whose rates and spectra are influenced by a variety of complex and interacting forces. Although DNA repair pathways are generally known to play key roles in maintaining genetic stability, much remains to be understood about the relative roles of different pathways in preventing the accumulation of mutations and the extent of heterogeneity in pathway-specific repair efficiencies across different genomic regions. In this study we examine mutation processes in base excision repair-deficient (nth-1) and nucleotide excision repair-deficient (xpa-1) Caenorhabditis elegans mutation-accumulation (MA) lines across 24 regions of the genome and compare our observations to previous data from mismatch repair-deficient (msh-2 and msh-6) and wild-type (N2) MA lines. Drastic variation in both average and locus-specific mutation rates, ranging two orders of magnitude for the latter, was detected among the four sets of repair-deficient MA lines. Our work provides critical insights into the relative roles of three DNA repair pathways in preventing C. elegans mutation accumulation and provides evidence for the presence of pathway-specific DNA repair territories in the C. elegans genome.