Activation of Oncogenic Super-Enhancers Is Coupled with DNA Repair by RAD51

Publication date: 15 October 2019Source: Cell Reports, Volume 29, Issue 3Author(s): Idit Hazan, Jonathan Monin, Britta A.M. Bouwman, Nicola Crosetto, Rami I. AqeilanSummaryDNA double-strand breaks (DSBs) are deleterious and tumorigenic but could also be essential for DNA-based processes. Yet the landscape of physiological DSBs and their role and repair are still elusive. Here, we mapped DSBs at high resolution in cancer and non-tumorigenic cells and found a transcription-coupled repair mechanism at oncogenic super-enhancers. At these super-enhancers the transcription factor TEAD4, together with various transcription factors and co-factors, co-localizes with the repair factor RAD51 of the homologous recombination pathway. Depletion of TEAD4 or RAD51 increases DSBs at RAD51/TEAD4 common binding sites within super-enhancers and decreases expression of related genes, which are mostly oncogenes. Co-localization of RAD51 with transcription factors at super-enhancers occurs in various cell types, suggesting a broad phenomenon. Together, our findings uncover a coupling between transcription and repair mechanisms at oncogenic super-enhancers, to control the hyper-transcription of multiple cancer drivers.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research