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Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice

The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in chann...

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Autores principales: Bellí, Gemma, Colomina, Neus, Castells-Roca, Laia, Lorite, Neus P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225081/
https://www.ncbi.nlm.nih.gov/pubmed/35736104
http://dx.doi.org/10.3390/jof8060621
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author Bellí, Gemma
Colomina, Neus
Castells-Roca, Laia
Lorite, Neus P.
author_facet Bellí, Gemma
Colomina, Neus
Castells-Roca, Laia
Lorite, Neus P.
author_sort Bellí, Gemma
collection PubMed
description The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in channeling DNA damage tolerance (DDT) and repair mechanisms to bypass unrepaired lesions and promote optimal fork replication restart. PCNA ubiquitination processes trigger the following two main DDT sub-pathways: Rad6/Rad18-dependent PCNA monoubiquitination and Ubc13-Mms2/Rad5-mediated PCNA polyubiquitination, promoting error-prone translation synthesis (TLS) or error-free template switch (TS) pathways, respectively. However, the fork protection mechanism leading to TS during fork reversal is still poorly understood. In contrast, PCNA sumoylation impedes the homologous recombination (HR)-mediated salvage recombination (SR) repair pathway. Focusing on Saccharomyces cerevisiae budding yeast, we summarized PCNA related-DDT and repair mechanisms that coordinately sustain genome stability and cell survival. In addition, we compared PCNA sequences from various fungal pathogens, considering recent advances in structural features. Importantly, the identification of PCNA epitopes may lead to potential fungal targets for antifungal drug development.
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spelling pubmed-92250812022-06-24 Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice Bellí, Gemma Colomina, Neus Castells-Roca, Laia Lorite, Neus P. J Fungi (Basel) Review The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in channeling DNA damage tolerance (DDT) and repair mechanisms to bypass unrepaired lesions and promote optimal fork replication restart. PCNA ubiquitination processes trigger the following two main DDT sub-pathways: Rad6/Rad18-dependent PCNA monoubiquitination and Ubc13-Mms2/Rad5-mediated PCNA polyubiquitination, promoting error-prone translation synthesis (TLS) or error-free template switch (TS) pathways, respectively. However, the fork protection mechanism leading to TS during fork reversal is still poorly understood. In contrast, PCNA sumoylation impedes the homologous recombination (HR)-mediated salvage recombination (SR) repair pathway. Focusing on Saccharomyces cerevisiae budding yeast, we summarized PCNA related-DDT and repair mechanisms that coordinately sustain genome stability and cell survival. In addition, we compared PCNA sequences from various fungal pathogens, considering recent advances in structural features. Importantly, the identification of PCNA epitopes may lead to potential fungal targets for antifungal drug development. MDPI 2022-06-10 /pmc/articles/PMC9225081/ /pubmed/35736104 http://dx.doi.org/10.3390/jof8060621 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bellí, Gemma
Colomina, Neus
Castells-Roca, Laia
Lorite, Neus P.
Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title_full Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title_fullStr Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title_full_unstemmed Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title_short Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
title_sort post-translational modifications of pcna: guiding for the best dna damage tolerance choice
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225081/
https://www.ncbi.nlm.nih.gov/pubmed/35736104
http://dx.doi.org/10.3390/jof8060621
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