Cell-cycle defect of DNA repair in progeria skin fibroblasts.
We examined the temporal regulation of DNA repair during synchronous cell proliferation in normal and progeroid human fibroblasts. Ultraviolet light-induced (254 nm, 20 J/m2) unscheduled DNA synthesis was measured at 4-h intervals after serum stimulation, for up to 32 h. Normal cells regulated DNA repair in a defined temporal sequence, showing a peak in the induction of DNA repair just before DNA synthesis. Progeroid skin fibroblasts failed to show an increase in nucleotide excision repair before scheduled DNA synthesis, but the background level of DNA repair was not significantly different from that in controls. Regulation of repair in progeroid human fibroblasts appeared similar, but not identical to that previously reported by Gupta and Sirover (1984b) for xeroderma pigmentosum complementation group C. Our results suggest that patients with Hutchinson-Gilford progeria may have a defect in DNA repair; the results offer nominal evidence that the average level of UV-induced DNA is decreased, and that individuals with this disease lack both the normal enhancement of DNA repair before scheduled DNA synthesis and the temporal control of DNA repair.
Lipman
J M
JM
National Center for Toxicological Research, Jefferson, AR 72079.
Applegate-Stevens
A
A
Soyka
L A
LA
Hart
R W
RW
D002453:Cell Cycle; D002460:Cell Line; D004260:DNA Repair / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D011371:Progeria / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014466:Ultraviolet Rays
D013936:Thymidine