Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/ncomms6513
Keywords
-
Categories
Funding
- National Institute of Health (NIH) [CA148629, GM087798, ES019498, ES021116, ES022291, GM099213, UL1-RR024153, Ul1TR000005]
- Dutch Cancer Society [NKI-2010-4877]
- National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1 TR0000005]
- NIH Roadmap for Medical Research
- UPCI Cancer Center Support Grant from the National Institutes of Health [CA047904]
- NATIONAL CANCER INSTITUTE [P30CA047904, R01CA148629] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000005] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024153] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R21ES022291, R44ES021116, R21ES019498, R43ES021116] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R43GM087798, R43GM099213, R44GM087798] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 beta (Pol beta) and XRCC1 is thought to facilitate repair by recruiting Pol beta 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 beta. 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 beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available