Differences in the regulation by poly(ADP-ribose) of repair of DNA damage from alkylating agents and ultraviolet light according to cell type.
Inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide in various human and hamster cells influenced the responses to DNA damage from methyl methanesulfonate, but not from ultraviolet light. After exposure to methyl methanesulfonate, 3-aminobenzamide increased the strand break frequency in all cell types studied, but only stimulated repair replication in lymphoid and HeLa cells, suggesting these are independent effects. 3-Aminobenzamide also inhibited the pathway for de novo synthesis of DNA purines, suggesting that some of its effects may be due to disturbance of precursor pathways and irrelevant to the role of poly(ADP-ribose) in repair. Previous claims that 3-aminobenzamide stimulates repair synthesis after exposure to UV light are probably artifacts, because the stimulations are only observed in lymphocytes in the presence of a high concentration of hydroxyurea that itself inhibits repair. The initial inhibition of semiconservative DNA synthesis and the excision of the major alkylation products and pyrimidine dimers were unaffected by 3-aminobenzamide. In general poly(ADP-ribose) synthesis appears to be uniquely involved in regulating the ligation stage of repair of alkylation damage but not ultraviolet damage. By regulating the ligation efficiency, poly(ADP-ribosylation) modulates the dynamic balance between incision and ligation, so as to minimize the frequency of DNA breaks. The ligation stage of repair of UV damage appears different and is not regulated by poly(ADP-ribosylation).
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis / Q000378:metabolism*; D014466:Ultraviolet Rays
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA; D008741:Methyl Methanesulfonate