Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae
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Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae. / Aguilera, Paula; Dubarry, Marion; Hardy, Julien; Lisby, Michael; Simon, Marie-Noëlle; Géli, Vincent.
I: EMBO Journal, Bind 41, Nr. 6, e108736, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae
AU - Aguilera, Paula
AU - Dubarry, Marion
AU - Hardy, Julien
AU - Lisby, Michael
AU - Simon, Marie-Noëlle
AU - Géli, Vincent
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - alternative lengthening of telomeres
KW - C-circles
KW - recombination
KW - senescence
KW - telomeres
U2 - 10.15252/embj.2021108736
DO - 10.15252/embj.2021108736
M3 - Journal article
C2 - 35147992
AN - SCOPUS:85124563059
VL - 41
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 6
M1 - e108736
ER -
ID: 298037371