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The nuclear pore complex prevents sister chromatid recombination during replicative senescence

Author

Listed:
  • Paula Aguilera

    (Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes Equipe labellisée Ligue)

  • Jenna Whalen

    (Tufts University)

  • Christopher Minguet

    (Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes Equipe labellisée Ligue)

  • Dmitri Churikov

    (Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes Equipe labellisée Ligue)

  • Catherine Freudenreich

    (Tufts University)

  • Marie-Noëlle Simon

    (Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes Equipe labellisée Ligue)

  • Vincent Géli

    (Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes Equipe labellisée Ligue)

Abstract

The Nuclear Pore Complex (NPC) has emerged as an important hub for processing various types of DNA damage. Here, we uncover that fusing a DNA binding domain to the NPC basket protein Nup1 reduces telomere relocalization to nuclear pores early after telomerase inactivation. This Nup1 modification also impairs the relocalization to the NPC of expanded CAG/CTG triplet repeats. Strikingly, telomerase negative cells bypass senescence when expressing this Nup1 modification by maintaining a minimal telomere length compatible with proliferation through rampant unequal exchanges between sister chromatids. We further report that a Nup1 mutant lacking 36 C-terminal residues recapitulates the phenotypes of the Nup1-LexA fusion indicating a direct role of Nup1 in the relocation of stalled forks to NPCs and restriction of error-prone recombination between repeated sequences. Our results reveal a new mode of telomere maintenance that could shed light on how 20% of cancer cells are maintained without telomerase or ALT.

Suggested Citation

  • Paula Aguilera & Jenna Whalen & Christopher Minguet & Dmitri Churikov & Catherine Freudenreich & Marie-Noëlle Simon & Vincent Géli, 2020. "The nuclear pore complex prevents sister chromatid recombination during replicative senescence," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13979-5
    DOI: 10.1038/s41467-019-13979-5
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    Cited by:

    1. Arianna Penzo & Marion Dubarry & Clémentine Brocas & Myriam Zheng & Raphaël M. Mangione & Mathieu Rougemaille & Coralie Goncalves & Ophélie Lautier & Domenico Libri & Marie-Noëlle Simon & Vincent Géli, 2023. "A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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