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Pré-Publication, Document De Travail Année : 2023

Cells limit mutagenesis by dealing with DNA lesions behind the fork

Katarzyna Maslowska

Résumé

DNA lesions are a threat for 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 nucleoMde directly opposite to the lesion, with the risk if introducing a mutaMon. Or errorfree Damage Avoidance (DA) that uses homologous recombinaMon to retrieve the geneMc informaMon from the sister chromaMd. In this arMcle, we invesMgate the Mming of lesion bypass. We show that TLS can occur at the fork, rapidly aaer the encounter with the blocking lesion. But TLS can also occur behind the fork, at postreplicaMve gaps that are generated downstream of the lesion aaer repriming has occurred. We show that in this laPer situaMon, TLS is reduced because it is in compeMMon with the Damage Avoidance pathway. We also showed that EXO1 seems to modulate the size of the post-replicaMve gaps, that in turn modulate the balance between TLS and damage avoidance.
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Dates et versions

hal-04271498 , version 1 (06-11-2023)

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Katarzyna Maslowska, Vincent Pagès. Cells limit mutagenesis by dealing with DNA lesions behind the fork. 2023. ⟨hal-04271498⟩

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