P09874

PARP-1(Poly(ADP-ribose) polymerase-1), also designated PARP, is a nuclear DNA-binding zinc finger protein that influences DNA repair, DNA replication, modulation of chromatin structure, and apoptosis. In response to genotoxic stress, PARP-1 catalyzes the transfer of ADP-ribose units from NAD(+) to a number of acceptor molecules including chromatin. PARP-1 recognizes DNA strand interruptions and can complex with RNA and negatively regulate transcription. Actinomycin D- and etoposide-dependent induction of caspases mediates cleavage of PARP-1 into a p89 fragment that traverses into the cytoplasm. Apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus is PARP-1-dependent and is necessary for PARP-1-dependent cell death. PARP-1 deficiencies lead to chromosomal instability due to higher frequencies of chromosome fusions and aneuploidy, suggesting that poly(ADP-ribosyl)ation contributes to the efficient maintenance of genome integrity.