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The chemical structure of poly(ADP-ribose) suggests not only that its modification of acceptor proteins should modify the structure and function of the acceptor proteins, but also that the poly(ADP-ribose) molecule itself should possess an intrinsic structural information that can alter cellular function(s).

Poly(ADP-ribose) polymerase (PARP) is conserved in eukaryotes. To analyze the function of PARP, we isolated and characterized the gene for PARP in Drosophila melanogaster. The PARP gene consisted of six translatable exons and spanned more than 50 kb. The DNA binding domain is encoded by exons 1-4. Although the consensus cleavage site of CED-3 like protease during apoptosis is conserved from human to Xenopus laevis PARPs, it is neither conserved in the corresponding region of Drosophila nor Sarcophaga peregrina. There are two cDNAs species in Drosophila. One cDNA could encode the full length PARP protein (PARP I), while the other is a truncated cDNA which could encode a partial-length PARP protein (PARP II), which lacks the automodification domain and is possibly produced by alternative splicing. The expression of these two forms of PARP in E. coli demonstrated that while PARP II has the catalytic NAD-binding domain and DNA-binding domain it is enzymatically inactive. On the other hand PARP I is active. A deletion mutant of PARP gene could grow to the end of embryogenesis but did not grow to the adult fly. These results suggest that the PARP gene plays an important function during the development of Drosophila.

Poly(ADP-ribose) is suggested to be involved in various physiological phenomena, such as DNA repair, sister chromatid exchanges, differentiation, proliferation and transformation of eukaryotic cells (1). To find a means of clarifying the biological function of poly(ADP-ribose), we purified poly(ADP-ribose) polymerase from human placenta. We also isolated the cDNA for poly(ADP-ribose) polymerase and determined the nucleotide sequence. Using the cDNA probe we found a decrease in the amount of transcript for the poly(ADP-ribose) polymerase gene during the retinoic acid-induced granulocytic differentiation of HL-60 cells.