Poly-ADP-ribosylation in health and disease

Abstract.

Poly(ADP-ribosyl)ation of proteins is involved in the regulation of basal cellular processes and seems to be crucial for genomic integrity and cell survival. Several nuclear poly(ADP-ribose) polymerases (PARPs) are known which interact with various proteins involved in DNA metabolism. These proteins can be targets of poly(ADP-ribosyl)ation, which generally downregulates their activities. Accordingly, PARPs have been implicated in numerous processes involving chromosomal DNA, such as the regulation of chromatin structure, DNA repair, replication and transcription. PARP-1, the major cellular PARP, and PARP-2 are activated by DNA strand breaks. These enzymes have been shown to participate in DNA repair. PARP-1 has also been associated with DNA replication and recombination. Another outstanding feature of PARP-1 is its impact on the activities of transcription factors and on gene expression. Two other nuclear PARP enzymes, tankyrase-1 and tankyrase-2, are important for telomere maintenance.