TY - JOUR
T1 - Nucleotide excision repair genes are expressed at low levels and are not detectably inducible in Caenorhabditis elegans somatic tissues, but their function is required for normal adult life after UVC exposure
AU - Boyd, Windy A.
AU - Crocker, Tracey L.
AU - Rodriguez, Ana M.
AU - Leung, Maxwell C.K.
AU - Wade Lehmann, D.
AU - Freedman, Jonathan H.
AU - Van Houten, Ben
AU - Meyer, Joel N.
N1 - Funding Information:
We thank Julie Rice and Daniel Snyder for technical assistance with COPAS Biosort experiments and C. elegans maintenance, Danica Ducharme of the NIEHS microarray facility for microarray work, and Marjolein Smith for statistical analysis of growth and feeding data. This work was supported by National Institutes of Health [P42 ES10356 to J.M.]; the National Toxicology Program [to W.B.]; and the Intramural Research Program of the National Institute of Environmental Health Sciences [to J.F.]. All nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Center for Research Resources.
PY - 2010/1/5
Y1 - 2010/1/5
N2 - We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6 J/m2/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m2/day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3 h after exposure to 50 J/m2 UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.
AB - We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6 J/m2/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m2/day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3 h after exposure to 50 J/m2 UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.
KW - Caenorhabditis elegans
KW - DNA damage response
KW - Gene-environment interaction
KW - Global gene expression
KW - Nucleotide excision repair
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U2 - 10.1016/j.mrfmmm.2009.10.008
DO - 10.1016/j.mrfmmm.2009.10.008
M3 - Article
C2 - 19879883
AN - SCOPUS:71549131286
SN - 0027-5107
VL - 683
SP - 57
EP - 67
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -