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.
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 6J/m(2)/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m(2)/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 3h after exposure to 50 J/m(2) 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.
Boyd
Windy A
WA
Biomolecular Screening Branch, National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Crocker
Tracey L
TL
Rodriguez
Ana M
AM
Leung
Maxwell C K
MC
Lehmann
D Wade
DW
Freedman
Jonathan H
JH
Van Houten
Ben
B
Meyer
Joel N
JN
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005854:Germ Cells; D052216:Glucagon-Like Peptide 1 / Q000235:genetics* / Q000378:metabolism; D006358:Hot Temperature; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012098:Reproduction / Q000528:radiation effects; D015996:Survival Rate; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D051760:Xeroderma Pigmentosum Group A Protein; D052216:Glucagon-Like Peptide 1; D045643:DNA Repair Enzymes