THE ROLE OF POLY(ADP-RIBOSYL)ATION IN THE ADAPTIVE RESPONSE

An involvement of the poly(ADP-ribosyl)ation system in the expression of the adaptive response has been demonstrated with inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase. This enzyme is a key compo nent of a reaction cycle in chromatin, involving dynamic synthesis and degradation of variably sized ADP-ribose polymers in response to DNA strand breaks. The present report reviews recent work focussing on the response of the poly(ADP-ribosyl)ation system in low dose adaptation. The results suggest that adaptation of human cells to minute concentr ations of an alkylating agent involves a different activation mechanis m for poly(ADP-ribose) polymerase than DNA break-mediated stimulation after high dose treatment. Moreover, adaptation induces the formation of branched polymers with a very high binding affinity for histone tai ls and selected other proteins. High dose challenge treatment of adapt ed cells further enhances formation of branched polymers. We propose t hat apart from sensing DNA nicks, poly(ADP-ribose) polymerase may be p art of pathway protecting cells from downstream events of DNA damage.