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

Idit Hazan, Jonathan Monin, Britta A.M. Bouwman, Nicola Crosetto, Rami I. Aqeilan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

By mapping physiological double-strand breaks (DSBs) of tumorigenic and non-tumorigenic cells Hazan et al. uncover a coupled transcription-repair mechanism at oncogenic super-enhancers in which RAD51 of the homologous recombination pathway plays a key role supporting the hyper-transcription of related oncogenes.

Original languageAmerican English
Pages (from-to)560-572.e4
JournalCell Reports
Volume29
Issue number3
DOIs
StatePublished - 15 Oct 2019

Bibliographical note

Funding Information:
We are grateful to the Aqeilan lab members for fruitful discussions and to Prof. Eran Meshorer and Prof. Itamar Simon from the Hebrew University of Jerusalem for critical reading of the manuscript. We would like to thank Moshe Roseman for assisting with data analysis and Dr. Abed Nasereddin and Dr. Idit Shiff from the Core Research Facility of the Hebrew University-Hadassah Medical School. We are thankful to Prof. Batsheva Kerem for providing us with BJ cells, Prof. Yuval Dor (HUJI) and Raphael Scharfmann (INSERM) for EndoC-β cells, Dr. Srinvasa Rao for primary mouse neuronal progenitors, and Reza Mirzazadeh (Crosetto lab) for initial help on BLISS. The Aqeilan lab is supported by the European Research Council (ERC) Consolidator Grant under the European Union ’s Horizon 2020 research and innovation program (grant agreement 682118 ) and by the Israel Science Foundation (ISF; grant agreement 1574/15 ).

Funding Information:
We are grateful to the Aqeilan lab members for fruitful discussions and to Prof. Eran Meshorer and Prof. Itamar Simon from the Hebrew University of Jerusalem for critical reading of the manuscript. We would like to thank Moshe Roseman for assisting with data analysis and Dr. Abed Nasereddin and Dr. Idit Shiff from the Core Research Facility of the Hebrew University-Hadassah Medical School. We are thankful to Prof. Batsheva Kerem for providing us with BJ cells, Prof. Yuval Dor (HUJI) and Raphael Scharfmann (INSERM) for EndoC-? cells, Dr. Srinvasa Rao for primary mouse neuronal progenitors, and Reza Mirzazadeh (Crosetto lab) for initial help on BLISS. The Aqeilan lab is supported by the European Research Council (ERC) Consolidator Grant under the European Union's Horizon 2020 research and innovation program (grant agreement 682118) and by the Israel Science Foundation (ISF; grant agreement 1574/15). I.H. designed and performed the experiments and wrote the manuscript. J.M. analyzed BLISS and ChIP-seq data. N.C. and B.A.M.B. developed the BLISS and sBLISS protocol. B.A.M.B. performed all sBLISS experiments. R.I.A. designed and supervised the experiments, was responsible for the overall project strategy and management, and wrote the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • AP-1 complex (JUN/FOS)
  • BLISS
  • DSBs
  • RAD51
  • TEAD4
  • super-enhancer
  • transcription

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