Abstract

Poly(ADP-ribosyl)ation is a posttranslational protein modification mediated by members of the poly(ADP-ribose) polymerase (PARP) family. The ADP-ribose polymers, synthesized by the diverse PARP enzymes by cleavage of NAD+, are involved in the regulation of multiple cellular functions. Presently, only a single enzyme, poly(ADP-ribose) glycohydrolase (PARG), has been identified that catalyzes hydrolysis of poly(ADP-ribose) in the cell, causing a rapid turnover of the biopolymer which may ultimately result in lethal depletion of cellular NAD+ pools. In this study, we describe the construction of the first human full-length PARG cDNA clone from reversely transcribed fibroblast RNA. Using a computational approach, the human PARG gene was mapped to chromosome 10 (10q11.23) as had been determined earlier by in situ hybridization, and the gene structure was characterized in detail. The complete open reading frame consists of 18 exons and 17 introns with exons 9 to 14 forming the catalytic center of the enzyme and exons 1 to 3 encoding the putative regulatory domain. We show that the human PARG gene shares a 470 bp common promoter region with a gene coding for a mitochondrial membrane translocase (TIM23) gene and that this gene arrangement is conserved in the murine genome. The recent evidence for involvement of PARP-1 in mitochondria dependent apoptosis by triggering AIF release raises the interesting possibility of a functional significance of the organization of the PARG and TIM23 genes.References: 1.Meyer RG, Meyer-Ficca ML, Jacobson EL, Jacobson MK: Human poly(ADP-ribose) glycohydrolase (PARG) gene structure and the common promoter sequence it shares with inner mitochondrial membrane translocase 23 (TIM23). 2003, Submitted

Keywords: PARG, PARP, Mitochondria, gene cloning, TIM23, promoter, gene structure