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Eukaryotic stress-induced mutagenesis is limited by a local control of translesion synthesis.

ABSTRACT: 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 work, 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 imperative for TLS to occur. More importantly, we show that the activation of the DDR 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.

SUBMITTER: Maslowska KH

PROVIDER: S-EPMC8887424 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Eukaryotic stress-induced mutagenesis is limited by a local control of translesion synthesis.

Masłowska Katarzyna H KH Villafañez Florencia F Laureti Luisa L Iwai Shigenori S Pagès Vincent V

Nucleic acids research 20220201 4

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 work, 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 ind ...[more]

PMID: 35104879

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