CLONING OF CDNA-ENCODING DROSOPHILA POLY(ADP-RIBOSE) POLYMERASE - LEUCINE ZIPPER IN THE AUTO-MODIFICATION DOMAIN

We have isolated cDNA clones for a Drosophila poly(ADP-ribose) polymer ase (PARP; EC 2.4.2.30) by screening a lambdagt11 cDNA library with a Drosophila partial cDNA fragment. The Drosophila PARP probe was obtain ed by the polymerase chain reaction with heterologous primers deduced from conserved amino acids in the mammalian, chicken, amphibian, and f ish sequences. The Drosophila PARP mRNA is 3.2 kb in length and is exp ressed in the early stages of development. The PARP protein of 994 ami no acids contains two zinc-finger motifs and an NAD-binding motif, whi ch are conserved among different species. Interestingly, the heptad le ucine repeat in an alpha-helix was found in Drosophila PARP. Alignment s of the auto-modification domains of various species showed the repea ted hydrophobic amino acids on the same face of the helix that make th e coiled-coil configuration in the mammalian and chicken sequences. Th e presence of a leucine-zipper motif in the auto-modification domain s uggests that this motif might be responsible for protein-protein inter action between PARP and physiological acceptors. PARP may have novel f unctions, possibly involving its homo- and/or heterodimerization with other nuclear leucine-zipper proteins and its regulation by ADP-ribosy lation.