HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase ?.

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 ? (Pol?) and XRCC1 is thought to facilitate repair by recruiting Pol? 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 Pol?. 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 Pol? 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.

SUBMITTER: Fang Q 

PROVIDER: S-EPMC4246423 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature