Role for non-homologous end-joining in the repair of UVA-induced DNA damage.
OBJECTIVE
The biological significance of long-wavelength ultraviolet (UV) light, UVA, is increasingly realized, but the precise nature of the cellular damage responsible for the effects of this radiation is still not clear. It has been reported that UVA can induce double-strand breaks in DNA, but the biological significance of these is not known. We have therefore examined the UVA sensitivity of a cell line deficient in non-homologous end-joining, the major pathway for the repair of DNA double-strand breaks in mammalian cells in order to determine the biological importance of UVA-induced DSB.


METHODS
Xrs-6, a Chinese hamster ovary cell line mutant for XRCC5 (Ku80) was compared with its parental CHO-K1 cell line for its sensitivity to UVA radiation (365 nm) using both a clonogenic assay and the micronucleus assay.


RESULTS
Xrs-6 cells were sensitive to the cytotoxic effects of UVA. This resulted in the formation of chromosome damage, as measured by the micronucleus assay, which this cell line was unable to repair.


CONCLUSIONS
Owing to the nature of the repair defect in these cells, these results imply that DNA double-strand breaks are produced in cells following UVA irradiation, that the non-homologous end-joining repair pathway is involved in their repair and that they are produced with sufficient frequency to have biological significance.
Fell
L J
LJ
Department of Biological Sciences, Institute of Environmental and Natural Sciences, Lancaster University, Lancaster LA1 4YW, UK.
Paul
N D
ND
McMillan
T J
TJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019457:Chromosome Breakage; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015162:Micronucleus Tests; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D010641:Phenotype
D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D004247:DNA