A Novel Role for the Ribosomal Protein RpL22 in Poly(ADP-ribose)polymerase 1-Dependent Transcriptional Regulation. Ernest Boamah, Alexei Tulin. Epigenetics and Progenitor Cells Program, Fox Chase Cancer Center, Philadelphia, PA.

   Poly (ADP-ribose) polymerase 1 (PARP1), a nuclear protein, induces transcriptional activation or repression primarily through its ability to synthesize ADP-ribose (ADP) polymers. PARP1 generates ADP polymers using nicotinamide adenine dinucleotide (NAD+) as a substrate. The mechanisms linking PARP1 and ADP modification to chromatin regulation is currently being investigated with promising discoveries. Importantly, PARP1 has been shown to modify multiple cellular targets; however PARP1 only interacts with a select group of proteins. How these interactions impact PARP1 transcriptional regulation remains less understood. We recently discovered that RpL22, a ribosomal protein, interacts with PARP1. In this study, we evaluate the interaction of RpL22 with PARP1 and examine how this interaction affects PARP1 transcriptional regulation specifically at the hsp70 locus. Using the Drosophila model system, we observe that disruption of RpL22, using a P-element insertion, dramatically reduces PARP1-dependent hsp70 activation when larvae are exposed to heatshock. We therefore generated transgenic flies expressing CFP-tagged RpL22 to further examine this interaction and the impact on PARP1 transcription. We observed, using immunofluorescence analysis, that RpL22 predominantly localizes within active chromatin. Additionally, chromatin immunoprecipitation analysis also shows an even distribution of RpL22 within the hsp70 locus prior to heatshock. Together, our preliminary analyses suggest that RpL22 localization on chromatin may influence PARP1 transcriptional regulation. Our overall objective is to investigate PARP1-interacting proteins and their impact on PARP1 transcriptional activity.