Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.
Journal Article (Journal Article)
Background
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.Results
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.Conclusion
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.Full Text
Duke Authors
Cited Authors
- Meyer, JN; Boyd, WA; Azzam, GA; Haugen, AC; Freedman, JH; Van Houten, B
Published Date
- January 1, 2007
Published In
Volume / Issue
- 8 / 5
Start / End Page
- R70 -
PubMed ID
- 17472752
Pubmed Central ID
- PMC1929140
Electronic International Standard Serial Number (EISSN)
- 1474-760X
International Standard Serial Number (ISSN)
- 1474-7596
Digital Object Identifier (DOI)
- 10.1186/gb-2007-8-5-r70
Language
- eng