Inhibitors of poly(adenosine diphosphate ribose) polymerase induce sister chromatid exchanges

The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity

“…Poly(ADP-ribosyl)ation alters the activity of the other acceptor proteins also, due to the high negative charge of the attached ADP-ribose. In case of the histones, this process leads to electrostatic repulsion between DNA and loosening up the chromatin structure thereby making genes more accessible for gene transcription (Oikawa et al 1980, Poirier et al 1982, Park et al 1983, Satoh & Lindahl 1992, Lautier et al 1993, Herceg et al 2001. The effect of PARP on the function of these proteins is carried out by non-covalent protein-protein interactions and by covalent poly(ADP-ribosylation) (for review see Virág & Szabó 2002).…”

ADP-ribosylation in in vitro Systems Synthesizing Adenovirus DNA

“…The compound has been shown to inhibit rejoining of DNA strand breaks in mouse lymphoblastoid cells (Durkacz et al, 1980(Durkacz et al, , 1981 and to induce sister chromatid exchange in Chinese hamster ovary cells (Oikawa et al, 1980). When this compound was added to the CK extracts at a concentration of 5 mM, there was apparently complete inhibition of ADP-ribosylation as measured by [14C]NAD labelling and analysis by SD~PAGE and autoradiography (Fig.…”

BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability

“…PARP1 and PARP2 activity are critical for the efficient processing of DNA SSBs, and recruitment of XRCC1 (Masson et al, 1998;Sanderson and Lindahl, 2002;El-Khamisy et al, 2003;Woodhouse and Dianov, 2008; Figure 1). In the setting of PARP inhibition, unrepaired SSBs accumulate and can cause replication fork collapse and DNA DSB equivalents upon entry into S-phase (Oikawa et al, 1980;Wang et al, 1997;Simbulan-Rosenthal et al, 1999). These lesions must be repaired, and replication forks restarted using HR-mediated DSBR pathways, or the cell will accumulate lethal levels of DNA breaks.…”

“…Consistent with this model, PARP1-deficient mice are viable and have a relatively mild phenotype. However, both PARP1 2/2 cells and normal cell treated with PARP inhibitors show an increased level of sister-chromatid exchange and increased HR-mediated repair of DNA DSBs during S-phase (Oikawa et al, 1980;Wang et al, 1997;Simbulan-Rosenthal et al, 1999). The standard model to explain the sensitivity of BRCA1 2/2 cells to PARP inhibitors invokes the effect on PARP inhibitors on SSB repair and subsequent generation of large amounts of stalled replication forks and DSB equivalents which are lethal to HR-defective cells (Helleday et al, 2005;Ashworth, 2008b; Figure 1).…”