Differential Role of Poly(ADP-ribose) polymerase in D. discoideum growth and development

In the current study we highlight the involvement of PARP during D. discoideum development. Oxidative stress affects expression of aca and cAR1 thus affecting aggregation. Although parp expression is not affected during oxidative stress but it is involved during normal development as confirmed by our PARP down-regulation studies. Constitutive PARP down-regulation resulted in blocked development while no effect was observed on D. discoideum growth. Interestingly, stage specific PARP down-regulation arrested development at the slug stage.These results emphasize that PARP is essential for complex differentiation and its function may be linked to multicellularity. This is the first report where the involvement of PARP during normal multicellular development in D. discoideum, an ancient eukaryote, is established which could be of evolutionary significance. Thus our study adds one more role to the multitasking function of PARP.Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage repair network. Gene disruption studies involving PARP have identified various roles of PARP in cellular responses to DNA damage. Parp-/- mice are resistant to DNA damage induced cell death suggesting the involvement of PARP in cell death through NAD+ depletion [1]. PARP is a DNA damage sensor which upon binding to damaged sites triggers transfer of long, linear or branched chains of poly(ADP-ribose) (PAR) onto various nuclear acceptor proteins, including itself at the expense of NAD+ [2]. PARP is also a mediator of cell death after ischemia, reperfusion injury and exposure to various DNA damaging agents [3]. PARP has been shown to promote caspase independent cell death via release of apoptosis inducing factor [4,5]. Recently PARP's role has been identified in cytochrome c release during NMDA induced excitotoxicity [6]. The oxidant- and free-radical mediated necrosis of pancreatic β-cells, neurons, thymocytes and other cell types can be prevented by PARP inhi