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SUMMARY:The role of telomeres and telomerase in stem cell biology\, cancer
  and ageing - Maria Blasco\, CNIO\, Madrid
DTSTART:20120719T120000Z
DTEND:20120719T130000Z
UID:TALK32828@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:Telomeres protect the chromosome ends from unscheduled DNA rep
 air and degradation. Telomeres are heterochromatic domains composed of rep
 etitive DNA (TTAGGG repeats) bound to an array of specialized proteins. Th
 e length of telomere repeats and the integrity of telomere-binding protein
 s are both important for telomere protection. Furthermore\, telomere lengt
 h and integrity are regulated by a number of epigenetic modifications\, th
 us pointing to a higher-order control of telomere function. We have recent
 ly discovered that telomeres are transcribed generating\, long\, non-codin
 g RNAs\, which remain associated to the telomeric chromatin and are likely
  to have an important role in the regulation of telomeres.\nWe have shown 
 in the past that telomere length and the catalytic component of telomerase
 \, Tert\, are critical determinants for the mobilization of stem cells. Th
 e effects of telomerase and telomere length on stem cell behavior anticipa
 te the premature aging and cancer phenotypes of telomerase mutant mice.  M
 ore recently\, we have used this information to generate long-lived mice.\
 nShelterin is the major protein complex bound to mammalian telomeres\, how
 ever\, its potential relevance for cancer and aging was not addressed to d
 ate. I will report on mice conditionally deleted for the shelterin protein
 s TRF1\, TPP1 and RAP1. The study of these mice demonstrate that dysfuncti
 on of a telomere-associated protein is sufficient to produce severe telome
 ric damage in the absence of telomere shortening\, resulting into prematur
 e tissue degeneration\, acquisition of chromosomal aberrations and initiat
 ion of neoplastic lesions. These new mouse models\, together with the telo
 merase-deficient mouse model\, are valuable tools to understand human path
 ologies produced by telomere dysfunction ("telopathies").\n
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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