Telomerase protects developing neurons against DNA damage-induced cell death.
In mitotic cells, telomerase adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) thereby maintaining their length and preventing cellular senescence. We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain. We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage. Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide. Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents. Emerging findings suggest that DNA damage may trigger the death of neurons during brain development and in neurodegenerative disorders. Our data therefore suggest roles for TERT in modulating such cell deaths.
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Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
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Mattson
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D020134:Catalytic Domain; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D059004:Topoisomerase I Inhibitors; D014162:Transfection
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D059004:Topoisomerase I Inhibitors; D005047:Etoposide; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; D002166:Camptothecin