title: Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.
abstract: The nematode Caenorhabditis elegans has been used extensively to study responses to DNA damage. In contrast, little is known about DNA repair in this organism. C. elegans is unusual in that it encodes few DNA glycosylases and the uracil-DNA glycosylase (UDG) encoded by the ung-1 gene is the only known UDG. C. elegans could therefore become a valuable model organism for studies of the genetic interaction networks involving base excision repair (BER). As a first step towards characterization of BER in C. elegans, we show that the UNG-1 protein is an active uracil-DNA glycosylase. We demonstrate that an ung-1 mutant has reduced ability to repair uracil-containing DNA but that an alternative Ugi-inhibited activity is present in ung-1 nuclear extracts. Finally, we demonstrate that ung-1 mutants show altered levels of apoptotic cell corpses formed in response to DNA damaging agents. Increased apoptosis in the ung-1 mutant in response to ionizing radiation (IR) suggests that UNG-1 contributes to repair of IR-induced DNA base damage in vivo. Following treatment with paraquat however, the apoptotic corpse-formation was reduced. Gene expression profiling suggests that this phenotype is a consequence of compensatory transcriptomic shifts that modulate oxidative stress responses in the mutant and not an effect of reduced DNA damage signaling.
authors.affiliation: University of Oslo, The Biotechnology Centre, Norway.
authors.forename: Hanne K
authors.initials: HK
authors.lastname: Skjeldam
authors.forename: Henok
authors.initials: H
authors.lastname: Kassahun
authors.forename: Oyvind
authors.initials: O
authors.lastname: Fensgård
authors.forename: Tanima
authors.initials: T
authors.lastname: SenGupta
authors.forename: Eshrat
authors.initials: E
authors.lastname: Babaie
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Lindvall
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Arczewska
authors.forename: Hilde
authors.initials: H
authors.lastname: Nilsen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D009154:Mutation; D010269:Paraquat / Q000494:pharmacology*; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051981:Uracil-DNA Glycosidase; D010269:Paraquat