New molecular insights into human telomere transcription and the ALTernative telomere maintenance mechanism
(2018)
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- Authors
- Supervisors
- Decottignies , Anabelle
- Abstract
- Telomeres are specialized structures protecting chromosome ends. They are made of telomeric DNA, the shelterin protein complex and TERRA telomeric-repeat containing RNA, a product of telomere transcription. Divisions of normal somatic cells progressively shorten telomeres while this is counteracted by the activation of telomerase in about 85% of human tumors or an alternative homologous-recombination based mechanism, dubbed ALT, in 5 10% of tumours. Since ALT is not active in normal cells, it represents an interesting target for cancer therapy. We first studied TERRA regulation and found that, both in vitro and in vivo, in human muscles, AMPK stimulates NRF1/PGC1α-dependent transcription of telomeres, thus linking telomeres to metabolism. Then, we identified TSPYL5 as a possible molecular target for ALT therapy as the protein is specifically required to protect POT1 shelterin protein from proteasome degradation in ALT+ cells through regulation of TPP1, its binding partner at telomeres.
- Affiliations
UCLouvain SSS/DDUV/GEPI - Epigénétique
Citations
Diman, A. (2018). New molecular insights into human telomere transcription and the ALTernative telomere maintenance mechanism. https://hdl.handle.net/2078.5/174432