Functional interaction between FOXO3a and ATM regulates DNA damage response Export

@article{citeulike:2622016, abstract = {The maintenance of genomic stability in cells is relentlessly challenged by environmental stresses that induce DNA breaks, which activate the DNA-damage pathway mediated by ataxia-telangiectasia mutated (ATM) and its downstream mediators to control damage-induced cell-cycle checkpoints and DNA repair1, 2, 3. Here, we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser 1981 and prompting its downstream mediators to form nuclear foci in response to DNA damage. Silencing FOXO3a in cells abrogates the formation of ATM-pS1981 and phospho-histone H2AX foci after DNA damage. Increasing FOXO3a in cells promotes ATM-regulated signalling, the intra-S-phase or G2–M cell-cycle checkpoints, and the repair of damaged DNA, whereas cells lacking FOXO3a did not trigger the DNA-repair mechanism after DNA damage. The carboxy-terminal domain of FOXO3a binds to the FAT domain of ATM, thereby contributing to the activation of ATM. These results suggest that ATM may be regulated directly by FOXO3a in the DNA-damage response.}, author = {Tsai, Wen-Bin and Chung, Young M. and Takahashi, Yoko and Xu, Zhaohui and Hu, Mickey C. T.}, citeulike-article-id = {2622016}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ncb1709}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ncb1709}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18344987}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18344987}, day = {16}, doi = {10.1038/ncb1709}, issn = {1465-7392}, journal = {Nature Cell Biology}, keywords = {atm, dna\_damage\_response, foxo3a}, month = {March}, number = {4}, pages = {460--467}, posted-at = {2009-11-04 18:33:29}, priority = {2}, publisher = {Nature Publishing Group}, title = {Functional interaction between FOXO3a and ATM regulates DNA damage response}, url = {http://dx.doi.org/10.1038/ncb1709}, volume = {10}, year = {2008} }

TY - JOUR ID - citeulike:2622016 L3 - citeulike-article-id:2622016 N2 - The maintenance of genomic stability in cells is relentlessly challenged by environmental stresses that induce DNA breaks, which activate the DNA-damage pathway mediated by ataxia-telangiectasia mutated (ATM) and its downstream mediators to control damage-induced cell-cycle checkpoints and DNA repair1, 2, 3. Here, we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser 1981 and prompting its downstream mediators to form nuclear foci in response to DNA damage. Silencing FOXO3a in cells abrogates the formation of ATM-pS1981 and phospho-histone H2AX foci after DNA damage. Increasing FOXO3a in cells promotes ATM-regulated signalling, the intra-S-phase or G2–M cell-cycle checkpoints, and the repair of damaged DNA, whereas cells lacking FOXO3a did not trigger the DNA-repair mechanism after DNA damage. The carboxy-terminal domain of FOXO3a binds to the FAT domain of ATM, thereby contributing to the activation of ATM. These results suggest that ATM may be regulated directly by FOXO3a in the DNA-damage response. IS - 4 JF - Nature Cell Biology SN - 1465-7392 EP - 467 TI - Functional interaction between FOXO3a and ATM regulates DNA damage response PB - Nature Publishing Group VL - 10 SP - 460 KW - atm KW - dna_damage_response KW - foxo3a AU - Tsai, Wen-Bin AU - Chung, Young AU - Takahashi, Yoko AU - Xu, Zhaohui AU - Hu, Mickey PY - 2008/03/16/ UR - http://dx.doi.org/10.1038/ncb1709 ER -