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Article Dans Une Revue Nucleic Acids Research Année : 2022

Eukaryotic stress induced mutagenesis is limited by a local control of Translesion Synthesis

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The DNA Damage Response (DDR) preserves the genetic integrity of the cell by sensing and repairing damages after a genotoxic stress. Translesion Synthesis (TLS), an error-prone DNA damage tolerance pathway, is controlled by PCNA ubiquitination. In this report, we raise the question whether TLS is controlled locally, or globally. Using a recently developed method that allows to follow the bypass of a single lesion inserted into the yeast genome, we show that: i) TLS is controlled locally at each individual lesion by PCNA ubiquitination, ii) a single lesion is enough to induce PCNA ubiquitination, and iii) PCNA ubiquitination is an imperative requirement for TLS to occur. More importantly, we show that global PCNA ubiquitination that follows a genotoxic stress does not increase TLS at individual lesions. We conclude that unlike the SOS response in bacteria, the eukaryotic DDR does not promote TLS and mutagenesis.
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hal-03413120 , version 1 (08-03-2022)

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Katarzyna Maslowska, Florencia Villafanez, Luisa Laureti, Shigenori Iwai, Vincent Pagès. Eukaryotic stress induced mutagenesis is limited by a local control of Translesion Synthesis. Nucleic Acids Research, 2022, 50 (4), pp.2074-2080. ⟨10.1093/nar/gkac044⟩. ⟨hal-03413120⟩
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