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HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase β

Author

Listed:
  • Qingming Fang

    (University of Pittsburgh School of Medicine
    Hillman Cancer Center, University of Pittsburgh Cancer Institute
    Present address: University of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, Alabama 36604, USA)

  • Burcu Inanc

    (The Netherlands Cancer Institute)

  • Sandy Schamus

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute)

  • Xiao-hong Wang

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute)

  • Leizhen Wei

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute
    University of Pittsburgh School of Medicine)

  • Ashley R. Brown

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute)

  • David Svilar

    (University of Pittsburgh School of Medicine
    Hillman Cancer Center, University of Pittsburgh Cancer Institute)

  • Kelsey F. Sugrue

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute
    Present address: Institute for Biomedical Sciences, The George Washington University, Ross Hall, 2300 Eye Street NW, Washington DC 20037, USA)

  • Eva M. Goellner

    (University of Pittsburgh School of Medicine
    Hillman Cancer Center, University of Pittsburgh Cancer Institute
    Present address: Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA)

  • Xuemei Zeng

    (Biomedical Mass Spectrometry Center, University of Pittsburgh Schools of the Health Sciences)

  • Nathan A. Yates

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute
    Biomedical Mass Spectrometry Center, University of Pittsburgh Schools of the Health Sciences
    University of Pittsburgh School of Medicine)

  • Li Lan

    (Hillman Cancer Center, University of Pittsburgh Cancer Institute
    University of Pittsburgh School of Medicine)

  • Conchita Vens

    (The Netherlands Cancer Institute
    The Netherlands Cancer Institute)

  • Robert W. Sobol

    (University of Pittsburgh School of Medicine
    Hillman Cancer Center, University of Pittsburgh Cancer Institute
    University of Pittsburgh Graduate School of Public Health
    Present address: University of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, Alabama 36604, USA)

Abstract

Cellular DNA repair processes are crucial to maintain genome stability and integrity. In DNA base excision repair, a tight heterodimer complex formed by DNA polymerase β (Polβ) and XRCC1 is thought to facilitate repair by recruiting Polβ to DNA damage sites. Here we show that disruption of the complex does not impact DNA damage response or DNA repair. Instead, the heterodimer formation is required to prevent ubiquitylation and degradation of Polβ. In contrast, the stability of the XRCC1 monomer is protected from CHIP-mediated ubiquitylation by interaction with the binding partner HSP90. In response to cellular proliferation and DNA damage, proteasome and HSP90-mediated regulation of Polβ and XRCC1 alters the DNA repair complex architecture. We propose that protein stability, mediated by DNA repair protein complex formation, functions as a regulatory mechanism for DNA repair pathway choice in the context of cell cycle progression and genome surveillance.

Suggested Citation

  • Qingming Fang & Burcu Inanc & Sandy Schamus & Xiao-hong Wang & Leizhen Wei & Ashley R. Brown & David Svilar & Kelsey F. Sugrue & Eva M. Goellner & Xuemei Zeng & Nathan A. Yates & Li Lan & Conchita Ven, 2014. "HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase β," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6513
    DOI: 10.1038/ncomms6513
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