title: In vivo repair of alkylating and oxidative DNA damage in the mitochondrial and nuclear genomes of wild-type and glycosylase-deficient Caenorhabditis elegans.
abstract: Base excision repair (BER) is an evolutionarily conserved DNA repair pathway that is critical for repair of many of the most common types of DNA damage generated both by endogenous metabolic pathways and exposure to exogenous stressors such as pollutants. Caenorhabditis elegans is an increasingly important model organism for the study of DNA damage-related processes including DNA repair, genotoxicity, and apoptosis, but BER is not well understood in this organism, and has not previously been measured in vivo. We report robust BER in the nuclear genome and slightly slower damage removal from the mitochondrial genome; in both cases the removal rates are comparable to those observed in mammals. However we could detect no deficiency in BER in the nth-1 strain, which carries a deletion in the only glycosylase yet described in C. elegans that repairs oxidative DNA damage. We also failed to detect increased lethality or growth inhibition in nth-1 nematodes after exposure to oxidative or alkylating damage, suggesting the existence of at least one additional as-yet undetected glycosylase.
authors.affiliation: Nicholas School of the Environment and Center for the Environmental Implications of Nanotechnology, Duke University, Durham, NC 27708-0328, USA.
authors.forename: Senyene E
authors.initials: SE
authors.lastname: Hunter
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Gustafson
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Margillo
authors.forename: Sean A
authors.initials: SA
authors.lastname: Lee
authors.forename: Ian T
authors.initials: IT
authors.lastname: Ryde
authors.forename: Joel N
authors.initials: JN
authors.lastname: Meyer
mesh_terms: D000478:Alkylation; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D018509:DNA, Helminth / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics*; D017353:Gene Deletion; D049751:Genome, Helminth; D054629:Genome, Mitochondrial; D010084:Oxidation-Reduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D004720:Endonucleases; D045647:DNA Glycosylases; C553373:NTH-1 protein, C elegans