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Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner

Author

Listed:
  • Silvia Peripolli

    (University College London)

  • Leticia Meneguello

    (University College London
    University College London)

  • Chiara Perrod

    (University College London)

  • Tanya Singh

    (University College London)

  • Harshil Patel

    (Francis Crick Institute)

  • Sazia T. Rahman

    (University College London)

  • Koshiro Kiso

    (University College London)

  • Peter Thorpe

    (Queen Mary University)

  • Vincenzo Calvanese

    (University College London)

  • Cosetta Bertoli

    (University College London)

  • Robertus A. M. de Bruin

    (University College London
    University College London)

Abstract

Oncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress.

Suggested Citation

  • Silvia Peripolli & Leticia Meneguello & Chiara Perrod & Tanya Singh & Harshil Patel & Sazia T. Rahman & Koshiro Kiso & Peter Thorpe & Vincenzo Calvanese & Cosetta Bertoli & Robertus A. M. de Bruin, 2024. "Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45955-z
    DOI: 10.1038/s41467-024-45955-z
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    References listed on IDEAS

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