Unusual levels of (ADP-ribose)n and DNA synthesis in ataxia telangiectasia cells following gamma-ray irradiation

Abstract

Poly (ADP-ribose) polymerase is a eukaryotic chromosomal enzyme which utilizes the ADP-ribose moiety of NAD to synthesize the nucleic acid homopolymer (ADP-ribose)n (ref. 1). The precise function of (ADP-ribose)n has not been fully established although it does covalently modify chromosomal proteins by ADP-ribosylation. Here we demonstrate that gamma-ray irradiation of lymphoblastoid cells from normal subjects results in depressed DNA synthesis and increased (ADP-ribose)n synthesis. Irradiation of lymphoblastoid cells from patients with the autosomal recessive disease ataxia telangiectasia (AT), however, failed to depress DNA synthesis and did not elevate (ADP-ribose)n levels. We have confirmed that (ADP-ribose)n is synthesized in response to DNA damage and we propose that this polymer may function in the recovery from DNA damage by suppressing DNA synthesis.