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Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):E926-33. doi: 10.1073/pnas.1106300109. Epub 2012 Mar 26.

Role of the translationally controlled tumor protein in DNA damage sensing and repair.

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  • 1Departments of Radiology, Pharmacology and Physiology, and Biochemistry and Molecular Biology, New Jersey Medical School Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.

Abstract

The translationally controlled tumor protein (TCTP) is essential for survival by mechanisms that as yet are incompletely defined. Here we describe an important role of TCTP in response to DNA damage. Upon exposure of normal human cells to low-dose γ rays, the TCTP protein level was greatly increased, with a significant enrichment in nuclei. TCTP up-regulation occurred in a manner dependent on ataxia-telangiectasia mutated (ATM) kinase and the DNA-dependent protein kinase and was associated with protective effects against DNA damage. In chromatin of irradiated cells, coimmunoprecipitation experiments showed that TCTP forms a complex with ATM and γH2A.X, in agreement with its distinct localization with the foci of the DNA damage-marker proteins γH2A.X, 53BP1, and P-ATM. In cells lacking TCTP, repair of chromosomal damage induced by γ rays was compromised significantly. TCTP also was shown to interact with p53 and the DNA-binding subunits, Ku70 and Ku80, of DNA-dependent protein kinase. TCTP knockdown led to decreased levels of Ku70 and Ku80 in nuclei of irradiated cells and attenuated their DNA-binding activity. It also attenuated the radiation-induced G(1) delay but prolonged the G(2) delay. TCTP therefore may play a critical role in maintaining genomic integrity in response to DNA-damaging agents.

PMID:
22451927
[PubMed - indexed for MEDLINE]
PMCID:
PMC3341051
Free PMC Article

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