RT Journal Article
T1 Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae.
A1 Aguilera, Paula
A1 Dubarry, Marion
A1 Hardy, Julien
A1 Lisby, Michael
A1 Simon, Marie-Noëlle
A1 Géli, Vincent
K1 C-circles
K1 alternative lengthening of telomeres
K1 recombination
K1 senescence
K1 telomeres
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.
YR 2022
FD 2022-02-11
LK http://hdl.handle.net/10668/21694
UL http://hdl.handle.net/10668/21694
LA en
DS RISalud
RD Apr 11, 2025