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Non-transcriptional control of DNA replication by c-Myc

Author

Listed:
  • David Dominguez-Sola

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Carol Y. Ying

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Carla Grandori

    (Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Present address: Rosetta Inpharmatics, Merck, Seattle, Washington 98109, USA.)

  • Luca Ruggiero

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Brenden Chen

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Muyang Li

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Denise A. Galloway

    (Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA)

  • Wei Gu

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Jean Gautier

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

  • Riccardo Dalla-Favera

    (Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA)

Abstract

The c-Myc proto-oncogene encodes a transcription factor that is essential for cell growth and proliferation and is broadly implicated in tumorigenesis. However, the biological functions required by c-Myc to induce oncogenesis remain elusive. Here we show that c-Myc has a direct role in the control of DNA replication. c-Myc interacts with the pre-replicative complex and localizes to early sites of DNA synthesis. Depletion of c-Myc from mammalian (human and mouse) cells as well as from Xenopus cell-free extracts, which are devoid of RNA transcription, demonstrates a non-transcriptional role for c-Myc in the initiation of DNA replication. Overexpression of c-Myc causes increased replication origin activity with subsequent DNA damage and checkpoint activation. These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and oncogenic functions.

Suggested Citation

  • David Dominguez-Sola & Carol Y. Ying & Carla Grandori & Luca Ruggiero & Brenden Chen & Muyang Li & Denise A. Galloway & Wei Gu & Jean Gautier & Riccardo Dalla-Favera, 2007. "Non-transcriptional control of DNA replication by c-Myc," Nature, Nature, vol. 448(7152), pages 445-451, July.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7152:d:10.1038_nature05953
    DOI: 10.1038/nature05953
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    Cited by:

    1. 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.
    2. Holger Schwender & Silvia Selinski & Meinolf Blaszkewicz & Rosemarie Marchan & Katja Ickstadt & Klaus Golka & Jan G Hengstler, 2012. "Distinct SNP Combinations Confer Susceptibility to Urinary Bladder Cancer in Smokers and Non-Smokers," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-12, December.
    3. Richard Nisa, 2015. "Capturing humanitarian war: the collusion of violence and care in US-managed military detention," Environment and Planning A, , vol. 47(11), pages 2276-2291, November.
    4. Laura Curti & Sara Rohban & Nicola Bianchi & Ottavio Croci & Adrian Andronache & Sara Barozzi & Michela Mattioli & Fernanda Ricci & Elena Pastori & Silvia Sberna & Simone Bellotti & Anna Accialini & R, 2024. "CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Wenting Zhang & Yue Wang & Yongjie Liu & Cuifang Liu & Yizhou Wang & Lin He & Xiao Cheng & Yani Peng & Lu Xia & Xiaodi Wu & Jiajing Wu & Yu Zhang & Luyang Sun & Ping Chen & Guohong Li & Qiang Tu & Jin, 2023. "NFIB facilitates replication licensing by acting as a genome organizer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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