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The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging

Nucleic Acids Res. 2022-02; 
Yilin Ying, Xuefei Hu, Peng Han, Aaron Mendez-Bermudez, Serge Bauwens, Rita Eid, Li Tan, Mélanie Pousse, Marie-Joseph Giraud-Panis, Yiming Lu, Eric Gilson, Jing Ye
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摘要

The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, resto... More

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