Poly(ADP-ribose) metabolism in ultraviolet irradiated human fibroblasts

• Published in: The Journal of biological chemistry Vol. 258; no. 1; pp. 103 - 107
• Main Authors: Jacobson, E L, Antol, K M, Juarez-Salinas, H, Jacobson, M K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-01-1983; American Society for Biochemistry and Molecular Biology
• Subjects: Cells, Cultured; Cytarabine - pharmacology; DNA Repair; DNA Replication - drug effects; DNA Replication - radiation effects; Fibroblasts - metabolism; Fibroblasts - radiation effects; Humans; Hydroxyurea - pharmacology; Infant, Newborn; Male; NAD - metabolism; NAD - radiation effects; Nucleoside Diphosphate Sugars - radiation effects; Poly Adenosine Diphosphate Ribose - metabolism; Poly Adenosine Diphosphate Ribose - radiation effects; Skin - drug effects; Skin - metabolism; Skin - radiation effects; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)33226-5

Exposure of human fibroblasts to 5 J/m2 of UV light resulted in a rapid increase of up to 1500% in the intracellular content of poly(ADP-ribose) and a rapid depletion of its metabolic precursor, NAD. When added just prior to UV treatment, the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, totally blocked both the increase of poly(ADP-ribose) and decrease in NAD for up to 2.5 h. Addition of 3-aminobenzamide at the time of maximal accumulation of poly(ADP-ribose) resulted in a decrease to basal levels with a half-life of approximately 6 min. The rates of accumulation of poly(ADP-ribose) and depletion of NAD were increased in the presence of either 1-beta-arabinofuranosylcytosine or hydroxyurea. Since these agents are known to cause an additional accumulation of DNA strand breaks following UV irradiation, these data provide evidence for a mechanism in which the rate of poly(ADP-ribose) synthesis following DNA damage is regulated in intact cells by the number of DNA strand breaks. Under conditions in which the synthesis of poly(ADP-ribose) was blocked, DNA repair replication induced by UV light was neither stimulated nor inhibited.