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

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

Authors :
Masłowska KH
Villafañez F
Laureti L
Iwai S
Pagès V
Source :
Nucleic acids research [Nucleic Acids Res] 2022 Feb 28; Vol. 50 (4), pp. 2074-2080.
Publication Year :
2022

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.<br /> (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Details

Language :
English
ISSN :
1362-4962
Volume :
50
Issue :
4
Database :
MEDLINE
Journal :
Nucleic acids research
Publication Type :
Academic Journal
Accession number :
35104879
Full Text :
https://doi.org/10.1093/nar/gkac044