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PMID: 17472752 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.

Genome biology ·Vol. 8 ·No. 5 ·2007-00-00 ·Pages R70

Meyer JN, Boyd WA, Azzam GA, Haugen AC, Freedman JH, Van Houten B

Abstract

Caenorhabditis elegans is an important model for the study of DNA damage and repair related processes such as aging, neurodegeneration, and carcinogenesis. However, DNA repair is poorly characterized in this organism. We adapted a quantitative polymerase chain reaction assay to characterize repair of DNA damage induced by ultraviolet type C (UVC) radiation in C. elegans, and then tested whether DNA repair rates were affected by age in adults. UVC radiation induced lesions in young adult C. elegans, with a slope of 0.4 to 0.5 lesions per 10 kilobases of DNA per 100 J/m2, in both nuclear and mitochondrial targets. L1 and dauer larvae were more than fivefold more sensitive to lesion formation than were young adults. Nuclear repair kinetics in a well expressed nuclear gene were biphasic in nongravid adult nematodes: a faster, first order (half-life about 16 hours) phase lasting approximately 24 hours and resulting in removal of about 60% of the photoproducts was followed by a much slower phase. Repair in ten nuclear DNA regions was 15% and 50% higher in more actively transcribed regions in young and aging adults, respectively. Finally, repair was reduced by 30% to 50% in each of the ten nuclear regions in aging adults. However, this decrease in repair could not be explained by a reduction in expression of nucleotide excision repair genes, and we present a plausible mechanism, based on gene expression data, to account for this decrease. Repair of UVC-induced DNA damage in C. elegans is similar kinetically and genetically to repair in humans. Furthermore, this important repair process slows significantly in aging C. elegans, the first whole organism in which this question has been addressed.

MeSH Terms
Aging/genetics Animals Caenorhabditis elegans DNA Damage DNA Repair/physiology Kinetics Polymerase Chain Reaction Ultraviolet Rays/adverse effects
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Meyer Joel N
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Alexander Drive, Research Triangle Park, NC 27709, USA. [email protected]
Boyd Windy A
Azzam Gregory A
Haugen Astrid C
Freedman Jonathan H
Van Houten Bennett
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2007-8-5-r70
Email
[email protected]
Published
2007-00-00
Pages
R70
Language
English
Region
England
NLM ID
100960660
PMCID
PMC1929140
Subset
IM
Grants
NIEHS NIH HHS · T32 ES007031 · United States
NIEHS NIH HHS · T32-ES-007031 · United States
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1186/gb-2007-8-5-r70 PMC Full Text View journal details
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