University of Cambridge > > Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer > The role of telomeres and telomerase in stem cell biology, cancer and ageing

The role of telomeres and telomerase in stem cell biology, cancer and ageing

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Telomeres protect the chromosome ends from unscheduled DNA repair and degradation. Telomeres are heterochromatic domains composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. The length of telomere repeats and the integrity of telomere-binding proteins are both important for telomere protection. Furthermore, telomere length and integrity are regulated by a number of epigenetic modifications, thus pointing to a higher-order control of telomere function. We have recently discovered that telomeres are transcribed generating, long, non-coding RNAs, which remain associated to the telomeric chromatin and are likely to have an important role in the regulation of telomeres. We have shown in the past that telomere length and the catalytic component of telomerase, Tert, are critical determinants for the mobilization of stem cells. The effects of telomerase and telomere length on stem cell behavior anticipate the premature aging and cancer phenotypes of telomerase mutant mice. More recently, we have used this information to generate long-lived mice. Shelterin is the major protein complex bound to mammalian telomeres, however, its potential relevance for cancer and aging was not addressed to date. I will report on mice conditionally deleted for the shelterin proteins TRF1 , TPP1 and RAP1 . The study of these mice demonstrate that dysfunction of a telomere-associated protein is sufficient to produce severe telomeric damage in the absence of telomere shortening, resulting into premature tissue degeneration, acquisition of chromosomal aberrations and initiation of neoplastic lesions. These new mouse models, together with the telomerase-deficient mouse model, are valuable tools to understand human pathologies produced by telomere dysfunction (“telopathies”).

This talk is part of the Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer series.

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