HSP90 Regulates DNA Repair Via the Interaction Between XRCC1 and DNA Polymerase β

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Nov 27

PMID 25423885

Citations 65

Authors

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

Affiliations

Soon will be listed here.

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.

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