Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase.

MYC is an oncogenic transcription factor that binds globally to active promoters and promotes transcriptional elongation by RNA polymerase II (RNAPII). Deregulated expression of the paralogous protein MYCN drives the development of neuronal and neuroendocrine tumours and is often associated with a particularly poor prognosis. Here we show that, similar to MYC, activation of MYCN in human neuroblastoma cells induces escape of RNAPII from promoters.

p53 Activity Results in DNA Replication Fork Processivity.

p53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. We report that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This is observed in tumor-derived U2OS cells but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion and in freshly isolated thymocytes from mice with differential p53 status.