Negative regulation of alkylation-induced sister-chromatid exchange by poly(ADP-ribose) polymerase-1 activity

One of the earliest responses to DNA damage in eukaryotic cells is activati on of poly(ADP-ribose) polymerase-1 (PARP-I), a DNA strand break-dependent nuclear enzyme which covalently modifies proteins with poly(ADP-ribose). He re, we show that conditional over-expression of PARP-1 in stably transfecte d hamster cells, which causes cellular over-accumulation of poly(ADP-ribose ) by several-fold, strongly suppresses alkylation-induced sister-chromatid exchange (SCE), while cytotoxicity of alkylation treatment is slightly enha nced. Viewed together with the known potentiation of SCE by abrogation of P ARP-1 activity, our results provide evidence that PARP-1 activity is an imp ortant regulator of alkylation-induced SCE formation, imposing a control th at is strictly negative and commensurate with the level of enzyme activity. Int. J. Cancer 88:351-355. 2000. (C) 2000 Wiley-Liss, Inc.