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Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication

Author

Listed:
  • Raffaella Di Micco

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Marzia Fumagalli

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Angelo Cicalese

    (European Institute of Oncology)

  • Sara Piccinin

    (Experimental Oncology 1, Centro di Riferimento Oncologico CRO IRCCS)

  • Patrizia Gasparini

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Chiara Luise

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Catherine Schurra

    (Genome Stability Unit, 75724 Pasteur Institute)

  • Massimiliano Garre’

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Paolo Giovanni Nuciforo

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

  • Aaron Bensimon

    (Genomic Vision)

  • Roberta Maestro

    (Experimental Oncology 1, Centro di Riferimento Oncologico CRO IRCCS)

  • Pier Giuseppe Pelicci

    (European Institute of Oncology)

  • Fabrizio d’Adda di Fagagna

    (IFOM Foundation – FIRC Institute of Molecular Oncology Foundation)

Abstract

Cancer and cell senescence Cancer is commonly thought of as uncontrolled cellular proliferation, but in the early stages of many cancers, oncogene expression is associated with cellular senescence. A possible explanation for this has now been found. Two groups report a link between oncogene-induced senescence and the DNA damage response. Activated oncogenes can cause aberrant DNA replication and thereby DNA damage that can lead to cell senescence. Cellular senescence was found previously to be a barrier to tumorigenesis in vivo, so oncogene-induced senescence may be an innate defence against cancer. But its effectiveness is often disabled by further mutations. Understanding the relationship between cell senescence and tumour formation may aid in the development of diagnostic and prognostic tools based on senescence markers.

Suggested Citation

  • Raffaella Di Micco & Marzia Fumagalli & Angelo Cicalese & Sara Piccinin & Patrizia Gasparini & Chiara Luise & Catherine Schurra & Massimiliano Garre’ & Paolo Giovanni Nuciforo & Aaron Bensimon & Rober, 2006. "Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication," Nature, Nature, vol. 444(7119), pages 638-642, November.
    • Handle: RePEc:nat:nature:v:444:y:2006:i:7119:d:10.1038_nature05327
    DOI: 10.1038/nature05327
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    Cited by:

    1. David Rombaut & Carine Lefèvre & Tony Rached & Sabrina Bondu & Anne Letessier & Raphael M. Mangione & Batoul Farhat & Auriane Lesieur-Pasquier & Daisy Castillo-Guzman & Ismael Boussaid & Chloé Friedri, 2024. "Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Revati Darp & Marc A. Vittoria & Neil J. Ganem & Craig J. Ceol, 2022. "Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Hervé Técher & Diyavarshini Gopaul & Jonathan Heuzé & Nail Bouzalmad & Baptiste Leray & Audrey Vernet & Clément Mettling & Jérôme Moreaux & Philippe Pasero & Yea-Lih Lin, 2024. "MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Sandra Buratta & Lorena Urbanelli & Krizia Sagini & Stefano Giovagnoli & Silvia Caponi & Daniele Fioretto & Nico Mitro & Donatella Caruso & Carla Emiliani, 2017. "Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-23, November.
    5. Wei Wu & Szymon A. Barwacz & Rahul Bhowmick & Katrine Lundgaard & Marisa M. Gonçalves Dinis & Malgorzata Clausen & Masato T. Kanemaki & Ying Liu, 2023. "Mitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Marc A. Vittoria & Nathan Kingston & Kristyna Kotynkova & Eric Xia & Rui Hong & Lee Huang & Shayna McDonald & Andrew Tilston-Lunel & Revati Darp & Joshua D. Campbell & Deborah Lang & Xiaowei Xu & Crai, 2022. "Inactivation of the Hippo tumor suppressor pathway promotes melanoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Jean-Philippe Coppé & Christopher K Patil & Francis Rodier & Yu Sun & Denise P Muñoz & Joshua Goldstein & Peter S Nelson & Pierre-Yves Desprez & Judith Campisi, 2008. "Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor," PLOS Biology, Public Library of Science, vol. 6(12), pages 1-1, December.
    8. Sascha Schäuble & Karolin Klement & Shiva Marthandan & Sandra Münch & Ines Heiland & Stefan Schuster & Peter Hemmerich & Stephan Diekmann, 2012. "Quantitative Model of Cell Cycle Arrest and Cellular Senescence in Primary Human Fibroblasts," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-14, August.

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