FIG. 6.

Domain structures of the human PARP family. A classification and a schematic comparison of protein structures of the six members of the bona fide PARP family, based on literature and database searches, are shown. The most significant domains detected have been indicated. The PRD domain is called the PARP regulatory domain and may be involved in regulation of the PARP-branching activity. The WGR domain is named after the most conserved central motif (W/G/R) of the domain. This motif is found in a variety of poly(A) polymerases and other proteins of unknown function. The BRCT domain is named after the breast cancer suppressor protein-1 (BRCA1) carboxy-terminal domain and is found within many DNA damage repair and cell cycle checkpoint proteins (446). The unique diversity of this domain superfamily allows BRCT modules to interact by forming homo- or hetero-BRCT multimers and phosphorylation-dependent BRCT-non-BRCT interactions (139, 446). The sterile alpha motif (SAM) is a widespread domain in signaling and nuclear proteins and mediates homo- or heterodimerization in many cases (reviewed in reference 20). The ankyrin repeat domains (ARD) mediate protein-protein interactions in very diverse families of proteins (279). The number of ankyrin repeats in a protein can range from 2 to over 20 (279). The vault protein inter-alpha-trypsin (VIT) and von Willebrand type A (vWA) domains are conserved domains found in all inter-alpha-trypsin inhibitor (ITI) family members (261). Although the exact roles of these domains remain unknown, they are presumed to be involved in mediating protein-protein interactions (261). ZF-I and ZF-II, PARP-1-type zinc finger domains (they can act as DNA nick sensors and general DNA-binding domains [161]); SAP, SAF/Acinus/PIAS-DNA-binding domain; LZM, putative leucine zipper-like motif; MVP-ID, major-vault particle interaction domain; NLS, nuclear localization signal; CLS, centriole-localization signal; HPS, His-Pro-Ser region.