Formation and repair of psoralen-DNA adducts and pyrimidine dimers in human DNA and chromatin.
DNA damage and repair in human cells exposed to ultraviolet light (254 nm) or to psoralen derivatives plus 360 nm light were compared by means of a variety of analytic techniques. The two kinds of damage show considerable structural similarity; both involve cyclobutyl bonds to 5,6 positions of pyrimidines as major products and have various minor products. In purified DNA, pyrimidine dimers, but not psoralen adducts, cause structural distortions that are substances for digestion with single-strand-specific nucleases. Whereas pyrimidine dimers are randomly produced in chromatin, psoralen adducts, are concentrated approximately 2- to 4-fold in linker regions of chromatin at doses that are not highly lethal. Chromatin shows considerable mobility; assignment of DNA to linker or core regions is not permanent, and psoralen adducts initially concentrated in linker regions become randomized after 10 hr. Pyrimidine dimers and psoralen adducts are excised by normal cells but not by repair-deficient xeroderma pigmentosum cells. This repair process requires DNA polymerase alpha, but its rate in ultraviolet-damaged cells is twice that in psoralen-damaged cells. Conversion of monoadducts to DNA-DNA crosslinks reduces the rate of repair because of the increased complexity of the damaged site.
D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004260:DNA Repair; D004720:Endonucleases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D011564:Furocoumarins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011740:Pyrimidine Dimers / Q000378:metabolism*; D015719:Single-Strand Specific DNA and RNA Endonucleases; D012867:Skin / Q000378:metabolism; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism
D002843:Chromatin; D011564:Furocoumarins; D011740:Pyrimidine Dimers; D004247:DNA; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases