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• W2077302783 startingPage "383" @default.
• W2077302783 abstract "Summary Dyskeratosis congenita (DC), an inherited bone marrow failure syndrome, is caused by defects in telomerase. Somatic cells from DC patients have shortened telomeres and clinical symptoms are most pronounced in organs with a high cell turnover, including those involved in hematopoiesis and skin function. We previously identified an autosomal dominant (AD) form of DC that is caused by mutations in the telomerase RNA component (TER). In this study, we evaluated whether retroviral expression of TER and/or telomerase reverse transcriptase (TERT), the catalytic component of telomerase, could extend telomere length and rescue AD DC cells from a phenotype characteristic of early senescence. Exogenous TER expression, without TERT, could not activate telomerase in AD DC skin fibroblasts. Transduction of TERT alone, however, provided AD DC cells with sufficient telomerase activity to extend average telomere length and proliferative capacity. Interestingly, we found that expression of TER and TERT together resulted in extension of lifespan and higher levels of telomerase and longer telomeres than expression of TERT alone in both AD DC and normal cells. Our results provide evidence that AD DC cells can be rescued from defects in telomere maintenance and proliferation, and that coexpression of TERT and TER together provides a more efficient means to elongate telomeres than expression of TERT alone. Similar strategies may be useful for ameliorating the detrimental effects of telomere shortening in AD DC and other diseases associated with telomerase or telomere defects." @default.
• W2077302783 created "2016-06-24" @default.
• W2077302783 creator A5020617631 @default.
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• W2077302783 creator A5068910414 @default.
• W2077302783 date "2007-02-19" @default.
• W2077302783 modified "2023-10-11" @default.
• W2077302783 title "Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts" @default.
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• W2077302783 doi "https://doi.org/10.1111/j.1474-9726.2007.00288.x" @default.
• W2077302783 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2225626" @default.
• W2077302783 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17381549" @default.
• W2077302783 hasPublicationYear "2007" @default.
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