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Control of DNA Damage Bypass by Ubiquitylation of PCNA

DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-...

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Autores principales: Ripley, Brittany M., Gildenberg, Melissa S., Washington, M. Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074500/
https://www.ncbi.nlm.nih.gov/pubmed/32013080
http://dx.doi.org/10.3390/genes11020138
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author Ripley, Brittany M.
Gildenberg, Melissa S.
Washington, M. Todd
author_facet Ripley, Brittany M.
Gildenberg, Melissa S.
Washington, M. Todd
author_sort Ripley, Brittany M.
collection PubMed
description DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.
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spelling pubmed-70745002020-03-20 Control of DNA Damage Bypass by Ubiquitylation of PCNA Ripley, Brittany M. Gildenberg, Melissa S. Washington, M. Todd Genes (Basel) Review DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways. MDPI 2020-01-29 /pmc/articles/PMC7074500/ /pubmed/32013080 http://dx.doi.org/10.3390/genes11020138 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ripley, Brittany M.
Gildenberg, Melissa S.
Washington, M. Todd
Control of DNA Damage Bypass by Ubiquitylation of PCNA
title Control of DNA Damage Bypass by Ubiquitylation of PCNA
title_full Control of DNA Damage Bypass by Ubiquitylation of PCNA
title_fullStr Control of DNA Damage Bypass by Ubiquitylation of PCNA
title_full_unstemmed Control of DNA Damage Bypass by Ubiquitylation of PCNA
title_short Control of DNA Damage Bypass by Ubiquitylation of PCNA
title_sort control of dna damage bypass by ubiquitylation of pcna
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074500/
https://www.ncbi.nlm.nih.gov/pubmed/32013080
http://dx.doi.org/10.3390/genes11020138
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