Poly(ADP-ribosylation) reduces the steady-state level of breaks in DNA following treatment of human cells with alkylating agents.
Following treatment of human fibroblasts with dimethyl-sulphate, more breaks persisted in DNA in cells incubated with 3-aminobenzamide, an inhibitor of ADP-ribosyltransferase, than in its absence. This effect of 3-aminobenzamide was more pronounced in non-dividing than in dividing cells. If non-dividing cells were treated with dimethylsulphate and then incubated for a few hours in the absence of 3-aminobenzamide, few breaks were detectable in the DNA. Subsequent addition of 3-aminobenzamide resulted in the reappearance of many breaks in the DNA. These data suggest that continued synthesis of poly(ADP-ribose) reduces the steady state level of breaks during excision repair of alkylation damage. This is probably mediated by the stimulation of DNA ligase activity. Inhibition of poly(ADP-ribose) synthesis with 3-aminobenzamide maintains or restores a higher steady-state level of breaks.
D000477:Alkylating Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases
D000477:Alkylating Agents; D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases