title: The relative roles of three DNA repair pathways in preventing Caenorhabditis elegans mutation accumulation.
abstract: 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.
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA. denver@cgrb.oregonstate.edu
authors.forename: Dee R
authors.initials: DR
authors.lastname: Denver
authors.forename: Seth
authors.initials: S
authors.lastname: Feinberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Steding
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Durbin
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000502:physiology*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics; D049751:Genome, Helminth; D005838:Genotype; D018095:Germ-Line Mutation; D008969:Molecular Sequence Data; D009154:Mutation; D015398:Signal Transduction; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D051760:Xeroderma Pigmentosum Group A Protein; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468347:NTHL1 protein, human; D045643:DNA Repair Enzymes