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Article Dans Une Revue EMBO Journal Année : 2022

Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae

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Résumé

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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Dates et versions

hal-03622415 , version 1 (21-11-2022)

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Paula Aguilera, Marion Dubarry, Julien Hardy, Michael Lisby, Marie-Noëlle Simon, et al.. Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae. EMBO Journal, 2022, 41 (6), ⟨10.15252/embj.2021108736⟩. ⟨hal-03622415⟩
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