Journal
CELL CYCLE
Volume 10, Issue 24, Pages 4300-4310Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.24.18642
Keywords
genomic stability; DNA repair; double-strand breaks; ATM; proteasome; PA28 gamma (PSME3)
Categories
Funding
- Israel Science Foundation
- A-T Medical Research Foundation
- Israel Cancer Research Fund
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health (NIH) [CA 50519]
- European Community [FP7/2007-2013, HEALTH-F2-2010-259893]
- Netherlands Genomics Initiative / Netherlands Organization for Scientific Research
Ask authors/readers for more resources
The DNA damage response (DDR) is a complex signaling network that leads to damage repair while modulating numerous cellular processes. DNA double-strand breaks (DSBs)-a highly cytotoxic DNA lesion-activate this system most vigorously. The DSB response network is orchestrated by the ATM protein kinase, which phosphorylates key players in its various branches. Proteasome-mediated protein degradation plays an important role in the proteome dynamics following DNA damage induction. Here, we identify the nuclear proteasome activator PA28 gamma (REG gamma; PSME3) as a novel DDR player. PA28 gamma depletion leads to cellular radiomimetic sensitivity and a marked delay in DSB repair. Specifically, PA28 gamma deficiency abrogates the balance between the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair. Furthermore, PA28 gamma is found to be an ATM target, being recruited to the DNA damage sites and required for rapid accumulation of proteasomes at these sites. Our data reveal a novel ATM-PA28 gamma-proteasome axis of the DDR that is required for timely coordination of DSB repair.
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