Fig. P1.

Role of TCTP in the DNA damage response. TCTP is up-regulated in the cytoplasm and nuclei of irradiated normal human cells, particularly following exposure to low doses of γ rays. It is regulated in an ATM- and DNA-PK–dependent manner. In the nuclei of irradiated cells, it exists in complex with the DNA-damage marker proteins ATM, p53, γH2A.X, Ku70, Ku80, filamin A, and heat-shock proteins (HSPs); it colocalizes with P-ATM, 53BP1, and γH2A.X foci, which are DNA damage-associated sites. TCTP knockdown attenuates the DNA-binding activity of Ku70 and Ku80, preventing normal repair of radiation-induced DNA damage. This knockdown also modulates the G₁ and G₂ cell-cycle checkpoints. HR, homologous recombination;IR, irradiation; NHEJ, nonhomologous end-joining.