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Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA
Translesion synthesis (TLS) is the mechanism by which DNA polymerases replicate through unrepaired DNA lesions. TLS is activated by monoubiquitination of the homotrimeric proliferating cell nuclear antigen (PCNA) at lysine-164, followed by the switch from replicative to specialized polymerases at DN...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621508/ https://www.ncbi.nlm.nih.gov/pubmed/26503230 http://dx.doi.org/10.1038/srep15759 |
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author | Lau, Wilson C. Y. Li, Yinyin Zhang, Qinfen Huen, Michael S. Y. |
author_facet | Lau, Wilson C. Y. Li, Yinyin Zhang, Qinfen Huen, Michael S. Y. |
author_sort | Lau, Wilson C. Y. |
collection | PubMed |
description | Translesion synthesis (TLS) is the mechanism by which DNA polymerases replicate through unrepaired DNA lesions. TLS is activated by monoubiquitination of the homotrimeric proliferating cell nuclear antigen (PCNA) at lysine-164, followed by the switch from replicative to specialized polymerases at DNA damage sites. Pol η belongs to the Y-Family of specialized polymerases that can efficiently bypass UV-induced lesions. Like other members of the Y-Family polymerases, its recruitment to the damaged sites is mediated by the interaction with monoubiquitinated PCNA (Ub-PCNA) via its ubiquitin-binding domain and non-canonical PCNA-interacting motif in the C-terminal region. The structural determinants underlying the direct recognition of Ub-PCNA by Pol η, or Y-Family polymerases in general, remain largely unknown. Here we report a structure of the Ub-PCNA/Pol η complex bound to DNA determined by single-particle electron microscopy (EM). The overall obtained structure resembles that of the editing PCNA/PolB complex. Analysis of the map revealed the conformation of ubiquitin that binds the C-terminal domain of Pol η. Our present study suggests that the Ub-PCNA/Pol η interaction requires the formation of a structured binding interface, which is dictated by the inherent flexibility of Ub-PCNA. |
format | Online Article Text |
id | pubmed-4621508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46215082015-10-29 Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA Lau, Wilson C. Y. Li, Yinyin Zhang, Qinfen Huen, Michael S. Y. Sci Rep Article Translesion synthesis (TLS) is the mechanism by which DNA polymerases replicate through unrepaired DNA lesions. TLS is activated by monoubiquitination of the homotrimeric proliferating cell nuclear antigen (PCNA) at lysine-164, followed by the switch from replicative to specialized polymerases at DNA damage sites. Pol η belongs to the Y-Family of specialized polymerases that can efficiently bypass UV-induced lesions. Like other members of the Y-Family polymerases, its recruitment to the damaged sites is mediated by the interaction with monoubiquitinated PCNA (Ub-PCNA) via its ubiquitin-binding domain and non-canonical PCNA-interacting motif in the C-terminal region. The structural determinants underlying the direct recognition of Ub-PCNA by Pol η, or Y-Family polymerases in general, remain largely unknown. Here we report a structure of the Ub-PCNA/Pol η complex bound to DNA determined by single-particle electron microscopy (EM). The overall obtained structure resembles that of the editing PCNA/PolB complex. Analysis of the map revealed the conformation of ubiquitin that binds the C-terminal domain of Pol η. Our present study suggests that the Ub-PCNA/Pol η interaction requires the formation of a structured binding interface, which is dictated by the inherent flexibility of Ub-PCNA. Nature Publishing Group 2015-10-27 /pmc/articles/PMC4621508/ /pubmed/26503230 http://dx.doi.org/10.1038/srep15759 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Lau, Wilson C. Y. Li, Yinyin Zhang, Qinfen Huen, Michael S. Y. Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title | Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title_full | Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title_fullStr | Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title_full_unstemmed | Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title_short | Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA |
title_sort | molecular architecture of the ub-pcna/pol η complex bound to dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621508/ https://www.ncbi.nlm.nih.gov/pubmed/26503230 http://dx.doi.org/10.1038/srep15759 |
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