13 Pages

Poly(ADP-ribose): Spectator or Participant in Excision Repair of DNA Damage

WithJ. E. Cleaver, W. J. Bodell, C. Borek, W. F. Morgan, J. L. Schwartz

Inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide in various human and hamster cell types influenced the responses to DNA damage from methyl methanesulfonate (MMS), but not from UV light. Excision of the major alkylation products and pyrimidine dimers was unaffected by 3-aminobenzamide. After exposure of cells to methyl methanesulfonate, 3-aminobenzamide increased the strand break frequency in all cell types studied, but stimulated repair replication only 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, particularly on repair replication, may be due to disturbance of precursor pathways. 3-Aminobenzamide stimulated sister chromatid exchange formation and mutagenesis but inhibited transformation, suggesting that some of these endpoints involve ADP-ribosylation by ways other than repair. Poly(ADP-ribose) synthesis appears to regulate the ligation stage of repair of alkylation damage by modulating a dynamic balance between incision and ligation, so as to minimize the frequency of DNA breaks.