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

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Preprint

    Submitted manuscript, 29 MB, PDF document

  • Paula Aguilera
  • Marion Dubarry
  • Julien Hardy
  • Lisby, Michael
  • Marie-Noëlle Simon
  • Vincent Géli

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.

Original languageEnglish
Article numbere108736
JournalEMBO Journal
Volume41
Issue number6
Number of pages14
ISSN0261-4189
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

    Research areas

  • alternative lengthening of telomeres, C-circles, recombination, senescence, telomeres

ID: 298037371