Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae
Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae
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DOI：
10.15252/embj.2021108736
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发表时间：
2022-02-11
期刊：
影响因子：
11.4
通讯作者：
Geli, Vincent
中科院分区：
文献类型：
--
作者：
Aguilera, Paula;Dubarry, Marion;Geli, Vincent
与人类细胞一样，酵母端粒可以通过被称为ALT(端粒替代延长)的重组机制在缺乏端粒酶活性的细胞中保持。ALT人类癌细胞的一个特征是称为C-环的染色体外端粒DNA元件，其来源和功能尚不清楚。在这里，我们表明，酵母中的染色体外端粒C-环可以在衰老危机后不久被检测到，并伴随着“II型”重组事件产生的幸存者的产生。我们发现C-环与核孔复合体(NPC)和SAGA-TREX2复合体结合，类似于其他非着丝粒上体DNA。破坏SAGA/TREX2复合体的完整性会影响C-环与NPC的结合和II型端粒重组，这表明C-环的NPC拴系促进了II型幸存者特有的长端粒重复的形成和/或传播。此外，我们发现核扩散障碍的破坏会损害II型重组。这些结果支持一个模型，在该模型中，C-环集中在NPC上有利于II型端粒重组，强调了空间协调在ALT型端粒维持机制中的重要性。
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.