Post-replicative lesion processing limits DNA damage-induced mutagenesis
Résumé
DNA lesions are a threat to genome stability. In order to cope with these lesions, cells have evolved lesion tolerance mechanisms: Translesion Synthesis (TLS) that allows the cell to insert a nucleotide directly opposite to the lesion, with the risk if introducing a mutation, and errorfree Damage Avoidance (DA) that uses homologous recombination to retrieve the genetic information from the sister chromatid.
In this article, we investigate the timing of lesion bypass. Our findings reveal that TLS can occur at the fork immediately after encountering the blocking lesion. However, TLS can also take place behind the fork, at post-replicative gaps that are generated downstream of the lesion after repriming. We show that in this latter situation, TLS compete with the Damage Avoidance pathway. Additionally, our study demonstrates that EXO1 nuclease influences the balance between TLS and DA by modulating the size of the post-replicative gaps.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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