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Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

Author

Listed:
  • Vassilis G. Gorgoulis

    (School of Medicine, University of Athens)

  • Leandros-Vassilios F. Vassiliou

    (School of Medicine, University of Athens)

  • Panagiotis Karakaidos

    (School of Medicine, University of Athens)

  • Panayotis Zacharatos

    (School of Medicine, University of Athens)

  • Athanassios Kotsinas

    (School of Medicine, University of Athens)

  • Triantafillos Liloglou

    (Cancer Research Center, University of Liverpool)

  • Monica Venere

    (The Wistar Institute
    Graduate Group in Biomedical Sciences)

  • Richard A. DiTullio

    (The Wistar Institute
    Graduate Group in Biomedical Sciences)

  • Nikolaos G. Kastrinakis

    (School of Medicine, University of Athens)

  • Brynn Levy

    (Mount Sinai School of Medicine)

  • Dimitris Kletsas

    (National Centre of Scientific Research ‘Demokritos’)

  • Akihiro Yoneta

    (The Wistar Institute)

  • Meenhard Herlyn

    (The Wistar Institute)

  • Christos Kittas

    (School of Medicine, University of Athens)

  • Thanos D. Halazonetis

    (The Wistar Institute
    University of Pennsylvania)

Abstract

Cancer checkpoint Two groups this week report findings that could have a big impact on our view of cancer development. Both looked at tumours (bladder, breast and colorectal, and in lung and skin) in various stages of progression for signs of a DNA damage response. And both find that early stages of cancer development are associated with an active DNA damage response and p53-dependent cell death. This suggests that the induction of a DNA damage response by oncogenic events is a potent tumour suppression mechanism, and explains the selective pressure for p53 mutations in precancerous lesions. Importantly, activation of the DNA damage checkpoint occurs before chromosome instability and malignancy. On the cover, 53BP1 foci in lung hyperplasia (green indicates DNA damage checkpoint activation).

Suggested Citation

  • Vassilis G. Gorgoulis & Leandros-Vassilios F. Vassiliou & Panagiotis Karakaidos & Panayotis Zacharatos & Athanassios Kotsinas & Triantafillos Liloglou & Monica Venere & Richard A. DiTullio & Nikolaos , 2005. "Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions," Nature, Nature, vol. 434(7035), pages 907-913, April.
    • Handle: RePEc:nat:nature:v:434:y:2005:i:7035:d:10.1038_nature03485
    DOI: 10.1038/nature03485
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    Cited by:

    1. Devashish Dwivedi & Daniela Harry & Patrick Meraldi, 2023. "Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jianbang Wang & Zhenzhen Li & Itamar Willner, 2022. "Cascaded dissipative DNAzyme-driven layered networks guide transient replication of coded-strands as gene models," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. 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.
    4. Simão, Éder M. & Cabral, Heleno B. & Castro, Mauro A.A. & Sinigaglia, Marialva & Mombach, José C.M. & Librelotto, Giovani R., 2010. "Modeling the Human Genome Maintenance network," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 389(19), pages 4188-4194.
    5. Tomoko Yamamori Morita & Jie Yu & Yukie Kashima & Ryo Kamata & Gaku Yamamoto & Tatsunori Minamide & Chiaki Mashima & Miyuki Yoshiya & Yuta Sakae & Toyohiro Yamauchi & Yumi Hakozaki & Shun-ichiro Kagey, 2023. "CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. 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.

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