TRF1 and telomerase dosage is crucial to face replication stress at telomeres
(2023) Course on Genome Instability and Human Disease- 5th edition — Location: Institut Curie, Paris (2.October.2023)
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- Abstract
- Telomeres are hard-to-replicate regions where fork progression is hampered by many obstacles, such as G-quadruplexes, RNA-DNA hybrids or the T-loop, and cannot be rescued by a converging fork. Many proteins help preventing telomere fragility and ensuring efficient telomere replication. Our project aims to further investigate how cells deal with replication stress at telomeres. We took advantage of a set of isogenic post-crisis survivors from E6/E7-immortalized human fibroblasts that spontaneously activated telomerase at various levels to investigate the genetic requirements of telomere replication. Evidences exist in mouse and yeast that telomerase can act on reversed forks at telomeres experiencing replication stress and new data suggest that telomerase can elongate reversed telomeric forks from a mini-chromosome introduced in human cells. Our data suggest that telomerase acts on the leading strand of naturally-occurring reversed forks provoking lagging strand fragility. We propose a model in which TRF1 and telomerase dosage is crucial to allow efficient replication of telomeres experiencing replication stress.
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Vaurs, M., Claude, E., Decottignies, A., & et al. (2023). TRF1 and telomerase dosage is crucial to face replication stress at telomeres. Course on Genome Instability and Human Disease- 5th edition, Institut Curie, Paris. https://hdl.handle.net/2078.5/247674