Repair of psoralen-induced cross-links and monoadducts in normal and repair-deficient human fibroblasts.
SV40-transformed normal, xeroderma pigmentosum (XP) and Fanconi's anemia (FA) fibroblasts have distinct repair capacities for monoadducts and DNA interstrand cross-links produced by exposure to near-UV (320-400 nm) light in the presence of 8-methoxypsoralen or angelicin. Excision repair of monoadducts occurred rapidly in normal and FA cells after exposure but not in XP cells. Cross-links were repaired in normal cells with a t1/2 of about 10 h but not in XP or FA cells. When the total number of adducts induced by 8-methoxypsoralen in normal cells was kept constant, the amount of repair replication decreased as the ratio of cross-links to monoadducts increased. This suggests either that cross-link repair is significantly different from monoadduct repair, involving smaller patches and a much slower rate of patching or that cross-links can inhibit monoadduct repair. Our results show that XP group A and FAH12 cell lines are deficient in cross-link repair. The data also suggest that the mechanism of cross-link repair in human cells involves several enzymes and that different ones may be deficient in XP and FA cells.
D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004260:DNA Repair; D004261:DNA Replication; D005199:Fanconi Anemia / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D011564:Furocoumarins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism
D011564:Furocoumarins; D004247:DNA