Journal
EMBO JOURNAL
Volume 41, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/embj.2021108736
Keywords
alternative lengthening of telomeres; C-circles; recombination; senescence; telomeres
Categories
Funding
- Region Provence-Alpes-Cote d'Azur/Inserm
- Fondation ARC pour la Recherche sur le Cancer
- Agence Nationale de Recherche [ANR-19-CE12-0023 NIRO]
- Ligue Nationale Contre le Cancer (Equipe labellisee)
- Agence Nationale de la Recherche (ANR) [ANR-19-CE12-0023] Funding Source: Agence Nationale de la Recherche (ANR)
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In yeast cells, C-circles bind to the nuclear pore complex (NPC) and the SAGA-TREX2 complex, promoting the formation of type II survivors. Disrupting the SAGA/TREX2 complex and the nuclear diffusion barrier affects telomere recombination.
As in human cells, yeast telomeres can be maintained in cells lacking telomerase activity by recombination-based mechanisms known as ALT (Alternative Lengthening of Telomeres). A hallmark of ALT human cancer cells are extrachromosomal telomeric DNA elements called C-circles, whose origin and function have remained unclear. Here, we show that extrachromosomal telomeric C-circles in yeast can be detected shortly after senescence crisis and concomitantly with the production of survivors arising from type II recombination events. We uncover that C-circles bind to the nuclear pore complex (NPC) and to the SAGA-TREX2 complex, similar to other non-centromeric episomal DNA. Disrupting the integrity of the SAGA/TREX2 complex affects both C-circle binding to NPCs and type II telomere recombination, suggesting that NPC tethering of C-circles facilitates formation and/or propagation of the long telomere repeats characteristic of type II survivors. Furthermore, we find that disruption of the nuclear diffusion barrier impairs type II recombination. These results support a model in which concentration of C-circles at NPCs benefits type II telomere recombination, highlighting the importance of spatial coordination in ALT-type mechanisms of telomere maintenance.
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