Poly(ADP-ribose) synthesis following DNA damage in cells heterozygous or homozygous for the xeroderma pigmentosum genotype.
Treatment of normal human cells with DNA-damaging agents such as UV light or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stimulates the conversion of NAD to the chromosomal polymer poly(ADP-ribose) which in turn results in a rapid depletion of the cellular NAD pool. We have studied the effect of UV light or MNNG on the NAD pools of seven cell lines of human fibroblasts either homozygous or heterozygous for the xeroderma pigmentosum genotype. Xeroderma pigmentosum cells of genetic complementation groups A, C, and D are deficient in the excision repair of DNA damage caused by UV light. Following UV treatment, the NAD content of these cells was unchanged (complementation groups A and D) or only slightly reduced (complementation group C). Xeroderma pigmentosum cells with the variant genotype have normal excision repair and UV treatment caused a large reduction in the size of the NAD pool. Cell lines derived from asymptomatic, parental heterozygotes of xeroderma pigmentosum complementation groups A and D showed an amount of lowering of NAD following UV treatment that was approximately one-half that of the control cell line. All of the cell lines are able to excise DNA damage caused by MNNG and all of the cell lines had a greatly reduced content of NAD following MNNG treatment. The results demonstrate a close relationship between the conversion of NAD to poly(ADP-ribose) and DNA excision repair in human cells.
D002460:Cell Line; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004260:DNA Repair; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism
D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA