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

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 Vens, Robert W. Sobol

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


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.

Original languageEnglish
Article number5513
JournalNature Communications
StatePublished - 2014

Bibliographical note

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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