Poly(ADP-ribose): A cellular signal of DNA damage

Exposure to high concentrations of 3-amino-benzamide (3AB) in various mammalian cells influences the responses to DNA damage from high doses of alkylating agents, but not from ultraviolet light. After exposure to methyl methane-sulfonate, 3AB increases the strand break frequency in all cell types studies, but only increases repair replication in lymphoid and HeLa cells, suggesting these are independent effects. The increased repair replication may only be due to pool disturbances, not a true increase in number or length of repair patches. 3AB also inhibited de novo synthesis of DNA purines. 3AB therefore disturbs precursor pathways and care must be exercised to distinguish this from a genuine role for poly(ADP-ribose) in repair. Poly(ADP-ribose) synthesis appears to regulate the ligation stage of repair of alkylation damage but not ultraviolet damage and modulate a dynamic balance between incision and ligation, so as to minimize the frequency of DNA breaks. Other effects of 3AB on transformation of radiation and chemically damaged cells, as well as its effects on differentiation and pool sizes, suggest complex roles for poly(ADP-ribose) in gene expression during development and carcinogenesis