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

Abstract
One of the earliest responses to DNA damage in eukaryotic cells is activation of poly(ADP‐ribose) polymerase‐1 (PARP‐1), a DNA strand break–dependent nuclear enzyme which covalently modifies proteins with poly(ADP‐ribose). Here, we show that conditional over‐expression of PARP‐1 in stably transfected 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 enhanced. Viewed together with the known potentiation of SCE by abrogation of PARP‐1 activity, our results provide evidence that PARP‐1 activity is an important regulator of alkylation‐induced SCE formation, imposing a control that is strictly negative and commensurate with the level of enzyme activity. Int. J. Cancer 88:351–355, 2000.

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