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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 Feb 2024
Historique:
received: 04 11 2020
accepted: 07 02 2024
medline: 22 2 2024
pubmed: 22 2 2024
entrez: 21 2 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 38383676
doi: 10.1038/s41467-024-45955-z
pii: 10.1038/s41467-024-45955-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1579

Subventions

Organisme : Cancer Research UK (CRUK)
ID : C37/A18784
Organisme : RCUK | Medical Research Council (MRC)
ID : Ref MC_U12266B
Organisme : Wellcome Trust (Wellcome)
ID : 221978/Z/20/Z

Informations de copyright

© 2024. The Author(s).

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Auteurs

Silvia Peripolli (S)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Leticia Meneguello (L)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.
UCL Cancer Institute, University College London, Gower Street, London, UK.

Chiara Perrod (C)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Tanya Singh (T)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Harshil Patel (H)

Francis Crick Institute, Midland Rd 1, London, UK.

Sazia T Rahman (ST)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Koshiro Kiso (K)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Peter Thorpe (P)

Queen Mary University, Mile End Road, London, UK.

Vincenzo Calvanese (V)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.

Cosetta Bertoli (C)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK. csttbrt@gmail.com.

Robertus A M de Bruin (RAM)

Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK. r.debruin@ucl.ac.uk.
UCL Cancer Institute, University College London, Gower Street, London, UK. r.debruin@ucl.ac.uk.

Classifications MeSH