Abstract
Poly(ADP-ribose) polymerase cDNAs have been isolated from different classes of animals. Cloning of genes from lower eukaryotes has allowed us to investigate directly the biological functions of poly(ADP-ribosyl)ation in vivo. The conservation of specific regions among mammals, chicken, Xenopus laevis, and Drosophila melanogaster reveals the essential structural elements required for recognition of breaks in DNA and for catalytic activity. Cys, His and basic residues in the zinc-finger consensus region are conserved. The carboxyl terminal region corresponding to an NAD-binding domain is strongly conserved. The dinucleotide-binding consensus sequence and beta 1-alpha A-beta 2, Rossmann fold structure, and beta-sheet structures are completely conserved from mammals to insect. In Drosophila, a putative leucine-zipper motif has been identified, and other poly(ADP-ribose) polymerases also contain an alpha-helical, amphipathic structure in the auto-modification domain. In this article, we review the recent structural analyses of the functional domains of poly(ADP-ribose) polymerase in phylogenetically divergent species, and discuss the implications of structural conservation for its biological functions.
