RRC ID 46674
Author Skjeldam HK, Kassahun H, Fensgård O, SenGupta T, Babaie E, Lindvall JM, Arczewska K, Nilsen H.
Title Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.
Journal DNA Repair (Amst.)
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.
Volume 9(8)
Pages 861-70
Published 2010-8-5
DOI 10.1016/j.dnarep.2010.04.009
PII S1568-7864(10)00145-X
PMID 20493785
MeSH Animals Apoptosis / radiation effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Damage / radiation effects DNA Repair / physiology* Gene Expression Profiling / methods Mutation* Paraquat / pharmacology* Uracil-DNA Glycosidase / genetics Uracil-DNA Glycosidase / metabolism*
IF 4.461
Times Cited 6
WOS Category TOXICOLOGY GENETICS & HEREDITY
Resource
C.elegans tm2862