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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/6/621 |
| _version_ | 1797485630394990592 |
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| author | Gemma Bellí Neus Colomina Laia Castells-Roca Neus P. Lorite |
| author_facet | Gemma Bellí Neus Colomina Laia Castells-Roca Neus P. Lorite |
| author_sort | Gemma Bellí |
| collection | DOAJ |
| 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 <i>Saccharomyces cerevisiae</i> 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. |
| first_indexed | 2024-03-09T23:22:00Z |
| format | Article |
| id | doaj.art-817baeb75dd94872b2f50d40d32a08cd |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T23:22:00Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-817baeb75dd94872b2f50d40d32a08cd2023-11-23T17:25:09ZengMDPI AGJournal of Fungi2309-608X2022-06-018662110.3390/jof8060621Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance ChoiceGemma Bellí0Neus Colomina1Laia Castells-Roca2Neus P. Lorite3Departament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, SpainThe 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 <i>Saccharomyces cerevisiae</i> 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.https://www.mdpi.com/2309-608X/8/6/621PCNADNA damage toleranceDNA replication stressfungal genome stabilityDNA replication forkspost-translational modifications |
| spellingShingle | Gemma Bellí Neus Colomina Laia Castells-Roca Neus P. Lorite Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice Journal of Fungi PCNA DNA damage tolerance DNA replication stress fungal genome stability DNA replication forks post-translational modifications |
| 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 | PCNA DNA damage tolerance DNA replication stress fungal genome stability DNA replication forks post-translational modifications |
| url | https://www.mdpi.com/2309-608X/8/6/621 |
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