PARP and CSB modulate the processing of transcription-mediated DNA strand breaks

Abstract

Topoisomerase 1 (Top1)-DNA cleavage complexes induced by camptothecin (CPT) cause DNA strand breaks during DNA replication or transcription. Although the cellular responses to replication-mediated DNA double-strand breaks have been well studied, the responses to transcription-mediated DNA strand breaks have not. Here, we show that poly (ADP-ribose) polymerase (PARP) and cockayne syndrome group B protein (CSB) modulate the CPT-induced formation of discrete p53-binding protein 1 (53BP1) nuclear foci at sites of transcription-mediated DNA strand breaks. Inhibition of PARP activity enhanced the formation of these foci, while knockdown of essential components of the base excision repair (BER) pathway did not. These findings suggest that PARP suppresses transcription-mediated 53BP1 foci formation, but that this does not occur through the BER pathway. In addition, knockdown of CSB, one of the key factors of transcription-coupled repair, slowed the kinetics of 53BP1 foci formation. These data suggest that PARP and CSB modulate the formation of 53BP1 foci during the processing of transcription-mediated DNA strand breaks.