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Involvement of the nuclear proteasome activator PA28 gamma in the cellular response to DNA double-strand breaks
- Source :
- Cell Cycle; Vol 10, Cell Cycle, 10(24), 4300-4310. Landes Bioscience
- Publication Year :
- 2011
- Publisher :
- Landes Bioscience, 2011.
-
Abstract
- 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.
- Subjects :
- Proteasome Endopeptidase Complex
DNA Repair
DNA damage
DNA repair
Immunoblotting
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Biology
Protein Serine-Threonine Kinases
DNA-binding protein
Autoantigens
Cell Line
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Report
Humans
Immunoprecipitation
DNA Breaks, Double-Stranded
RNA, Small Interfering
Molecular Biology
030304 developmental biology
0303 health sciences
Activator (genetics)
Tumor Suppressor Proteins
Cell Biology
DNA repair protein XRCC4
Flow Cytometry
Molecular biology
Cell biology
DNA-Binding Proteins
chemistry
Proteasome
030220 oncology & carcinogenesis
RNA Interference
DNA
Developmental Biology
Signal Transduction
Subjects
Details
- ISSN :
- 15514005 and 15384101
- Volume :
- 10
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Cell Cycle
- Accession number :
- edsair.doi.dedup.....725ac830f1414967a76ce88ec27d8fe3