Rap1-dependent replication stress at telomeres induces relocalization to the Nuclear Pore Complexes - Fédération de Recherche BioEnviS, BioEnvironnement et Santé (Université de Lyon)
Pré-Publication, Document De Travail (Preprint/Prepublication) Année : 2024

Rap1-dependent replication stress at telomeres induces relocalization to the Nuclear Pore Complexes

Résumé

Nuclear pore complexes (NPCs) have emerged as a key structure in the spatial regulation of DNA damage repair, including at replication forks that are slowed down or stalled at various obstacles. Here, we show that interstitial telomeric sequence (ITS) and natural telomeres interact with the NPCs during their replication. This localization is entirely dependent on the tight binding of Rap1 as a modified ITS that poorly bind Rap1 does not interact with NPCs. As with other types of replication barriers, ITS localization to NPCs is dependent on Mre11 and on the SUMO pathway. In addition, we identified the PCNA loader Ctf18 as essential for ITS localization to NPCs, and showed that its function is mediated by Scc2-dependent de novo cohesin loading at the replication fork. We also found that Mrc1, which acts in the same de novo cohesin loading pathway as Ctf18, contributes to ITS localization to NPCs, independently of its checkpoint function. In addition, we uncovered a role for Sir4, which is involved in heterochromatin formation at telomeres, in the tethering of ITS to NPCs. We propose that localization to NPCs in S phase is initially triggered by single-stranded DNA at paused forks, which induces a SUMOylation wave, de novo cohesin loading and chromatin compaction. This, in turn, would limit resection, avoid checkpoint activation and possibly favor error-free restart of the replication fork.
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Dates et versions

hal-04738115 , version 1 (15-10-2024)

Identifiants

  • HAL Id : hal-04738115 , version 1

Citer

Mohamad Al Hajj, Manon Pierre, Marion Dubarry, Michael Chang, Vincent Géli, et al.. Rap1-dependent replication stress at telomeres induces relocalization to the Nuclear Pore Complexes. 2024. ⟨hal-04738115⟩
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