Role of the insulin-like growth factor I/insulin receptor substrate 1 axis in Rad51 trafficking and DNA repair by homologous recombination.
The receptor for insulin-like growth factor I (IGF-IR) controls normal and pathological growth of cells. DNA repair pathways represent an unexplored target through which the IGF-IR signaling system might support pathological growth leading to cellular transformation. However, this study demonstrates that IGF-I stimulation supports homologous recombination-directed DNA repair (HRR). This ... effect involves an interaction between Rad51 and the major IGF-IR signaling molecule, insulin receptor substrate 1 (IRS-1). The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-I-mediated IRS-1 tyrosine phosphorylation. In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished. These results point to a direct role of IRS-1 in HRR and suggest a novel role for the IGF-IR/IRS-1 axis in supporting the stability of the genome.
Mesh Terms:
Animals, Antineoplastic Agents, Cell Line, Cell Survival, Cisplatin, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Humans, Insulin Receptor Substrate Proteins, Insulin-Like Growth Factor I, Mice, Phosphoproteins, Protein Binding, Protein Transport, Rad51 Recombinase, Receptor, IGF Type 1, Receptor, Insulin, Recombination, Genetic, Signal Transduction
Animals, Antineoplastic Agents, Cell Line, Cell Survival, Cisplatin, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Humans, Insulin Receptor Substrate Proteins, Insulin-Like Growth Factor I, Mice, Phosphoproteins, Protein Binding, Protein Transport, Rad51 Recombinase, Receptor, IGF Type 1, Receptor, Insulin, Recombination, Genetic, Signal Transduction
Mol. Cell. Biol.
Date: Nov. 01, 2003
PubMed ID: 14559999
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