The time course of repair of ultraviolet-induced DNA damage; implications for the structural organisation of repair.
Alternative molecular mechanisms can be envisaged for the cellular repair of UV-damaged DNA. In the "random collision" model, DNA damage distributed throughout the genome is recognised and repaired by a process of random collision between DNA damage and repair enzymes. The other model assumes a "processive" mechanism, whereby DNA is scanned for damage by a repair complex moving steadily along its length. These two models give different predictions concerning the time course of repair. Random collision should result in a declining rate of repair with time as the concentration of lesions in the DNA falls; but the processive model predicts a constant rate of repair until scanning is complete. We have examined the time course of DNA repair in human fibroblasts given low (generally sublethal) doses of UV light. Using 3 distinct assays, we find no sign of a constant repair rate after 4 J/m2 or less, even when the first few hours after irradiation are examined. Thus DNA repair is likely to depend on random collision. The implications of this finding for the structural organisation of repair are discussed.
D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair; D004278:DNA, Superhelical / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects; D007700:Kinetics; D008954:Models, Biological; D009707:Nucleosomes / Q000648:ultrastructure; D011740:Pyrimidine Dimers / Q000378:metabolism*; D013269:Stochastic Processes; D014466:Ultraviolet Rays
D004278:DNA, Superhelical; D009707:Nucleosomes; D011740:Pyrimidine Dimers; D011088:DNA Ligases