The cell cycle inhibitor p21CDKN1A was previously found to interact directly with DNA nick-sensor poly(ADP-ribose) polymerase-1 (PARP-1) and to promote base excision repair (BER). However, the molecular mechanism responsible for this BER-related association of p21 with PARP-1 remains to be clarified. In this study we investigate the capability of p21 to influence PARP-1 binding to DNA repair in...

Treatment of metastatic prostate cancer has evolved significantly over the past decade. Palliative therapy has, historically, consisted androgen deprivation, chemotherapy and different radiation approaches. More recently, breakthrough with use poly-ADP-ribose polymerase (PARP) inhibitors led to significant improvement in outcome patients who harbor certain genetic mutations. This concise review...

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central important functions PARP enzymes in DNA damage response nucleosome remodelling. Activation happens through binding via zinc fin...

PARP-1 is the most abundantly expressed member of a family of proteins that catalyze the transfer of ADP-ribose units from NAD+ to target proteins. Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PARP-1 binds in a specific manner to nucleosomes and modulates chromatin ...

Type 2 diabetes mellitus (T2DM) is associated with microvascular dysfunction. We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM. T2DM (db /db ) and nondiabetic control (db /db ) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks. Isolated coronary...

A transient, sublethal ischemic interval confers resistance to a subsequent, otherwise lethal ischemic insult, in a process termed ischemic preconditioning. Poly(ADP-ribose) polymerase-1 (PARP-1) normally functions in DNA repair, but extensive PARP-1 activation is a major cause of ischemic cell death. Because PARP-1 can be cleaved and inactivated by caspases, we investigated the possibility tha...

BACKGROUND AND PURPOSE Emerging data suggest that the molecular cell death pathways triggered by ischemic insults differ in the male and female brain. Cell death in males is initiated by poly(ADP-ribose) polymerase-1 (PARP-1) activation; however, manipulation of this pathway paradoxically increases ischemic damage in females. In contrast, females are exquisitely sensitive to caspase-mediated ce...

The use of poly (ADP-ribose) polymerase (PARP) inhibitors has recently increased as a result demonstrating their superior efficacy compared to traditional chemotherapy in various cancer subtypes many preclinical studies and clinical trials. A better understanding the molecular mechanisms PARP underlying foci that can be used screening markers for potential new therapeutic options would aid rati...

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) has been implicated in ischemia-reperfusion injury in many tissues under normothermic conditions. The purpose of this study was to determine whether PARP contributes to mechanisms of the hypothermic ischemia-reperfusion injury that occurs when kidneys are cold stored for transplantation. Cortical tissue slice PARP enzyme activity rose signif...

Poly(ADP-ribose) polymerase (PARP) transfers ADP ribose groups from NAD(+) to nuclear proteins after activation by DNA strand breaks. PARP overactivation by massive DNA damage causes cell death via NAD(+) and ATP depletion. Heretofore, PARP has been thought to be inactive under basal physiologic conditions. We now report high basal levels of PARP activity and DNA strand breaks in discrete neuro...