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Article Dans Une Revue Cell Reports Année : 2020

Telomerase Repairs Collapsed Replication Forks at Telomeres

Résumé

Telomeres are difficult-to-replicate sites whereby replication itself may threaten telomere integrity. We investigate, in fission yeast, telomere replication dynamics in telomerase-negative cells to unmask problems associated with telomere replication. Two-dimensional gel analysis reveals that replication of telomeres is severely impaired and correlates with an accumulation of replication intermediates that arises from stalled and collapsed forks. In the absence of telomerase, Rad51, Mre11-Rad50-Nbs1 (MRN) complex, and its co-factor CtIPCtp1 become critical to maintain telomeres, indicating that homologous recombination processes these intermediates to facilitate fork restart. We further show that a catalytically dead mutant of telomerase prevents Ku recruitment to telomeres, suggesting that telomerase and Ku both compete for the binding of telomeric-free DNA ends that are likely to originate from a reversed fork. We infer that Ku removal at collapsed telomeric forks allows telomerase to repair broken telomeres, thereby shielding telomeres from homologous recombination.
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Dates et versions

hal-02505864 , version 1 (11-03-2020)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Samah Matmati, Sarah Lambert, Vincent Geli, Stephane Coulon. Telomerase Repairs Collapsed Replication Forks at Telomeres. Cell Reports, 2020, 30 (10), pp.3312 - 3322. ⟨10.1016/j.celrep.2020.02.065⟩. ⟨hal-02505864⟩
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