The P53 tumor suppressor regulates the transcrip-tion initiation of selected genes by binding to specif-ic DNA sequences at their promoters. Here we report a novel role of P53 in transcription elongation in human cells. Upon transcription elongation block-age P53 is associated with genes, which have not been reported earlier as its direct targets. P53 could be co-immunoprecipitated with active forms of RPB1, highlighting its association with the elongat-ing RNAPII. During normal transcription cycle, P53 and RPB1 localized at distinct regions of selected non-canonical P53-target genes and this pattern of localization was changed upon transcription elonga-tion block. Additionally, transcription elongation block induced the ubiquitylation and the proteo-somal degradation of RPB1. Finally, we showed that the transcription block induced RPB1 degradation is mediated by P53. Our results reveal a novel role of P53 in human cells during transcription elongation blockage that might serve to facilitate the removal of RNAPII from DNA
