A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA

Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches...

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Autores principales: Yates, Luke A., Aramayo, Ricardo J., Pokhrel, Nilisha, Caldwell, Colleen C., Kaplan, Joshua A., Perera, Rajika L., Spies, Maria, Antony, Edwin, Zhang, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303327/
https://www.ncbi.nlm.nih.gov/pubmed/30575763
http://dx.doi.org/10.1038/s41467-018-07883-7
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author Yates, Luke A.
Aramayo, Ricardo J.
Pokhrel, Nilisha
Caldwell, Colleen C.
Kaplan, Joshua A.
Perera, Rajika L.
Spies, Maria
Antony, Edwin
Zhang, Xiaodong
author_facet Yates, Luke A.
Aramayo, Ricardo J.
Pokhrel, Nilisha
Caldwell, Colleen C.
Kaplan, Joshua A.
Perera, Rajika L.
Spies, Maria
Antony, Edwin
Zhang, Xiaodong
author_sort Yates, Luke A.
collection PubMed
description Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood. Using cryo electron microscopy we obtained a 3D reconstruction of the RPA trimerisation core bound with ssDNA (∼55 kDa) at ∼4.7 Å resolution and a dimeric RPA assembly on ssDNA. FRET-based solution studies reveal dynamic rearrangements of DBDs during coordinated RPA binding and this activity is regulated by phosphorylation at S178 in RPA70. We present a structural model on how dynamic DBDs promote the cooperative assembly of multiple RPAs on long ssDNA.
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spelling pubmed-63033272018-12-23 A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA Yates, Luke A. Aramayo, Ricardo J. Pokhrel, Nilisha Caldwell, Colleen C. Kaplan, Joshua A. Perera, Rajika L. Spies, Maria Antony, Edwin Zhang, Xiaodong Nat Commun Article Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood. Using cryo electron microscopy we obtained a 3D reconstruction of the RPA trimerisation core bound with ssDNA (∼55 kDa) at ∼4.7 Å resolution and a dimeric RPA assembly on ssDNA. FRET-based solution studies reveal dynamic rearrangements of DBDs during coordinated RPA binding and this activity is regulated by phosphorylation at S178 in RPA70. We present a structural model on how dynamic DBDs promote the cooperative assembly of multiple RPAs on long ssDNA. Nature Publishing Group UK 2018-12-21 /pmc/articles/PMC6303327/ /pubmed/30575763 http://dx.doi.org/10.1038/s41467-018-07883-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yates, Luke A.
Aramayo, Ricardo J.
Pokhrel, Nilisha
Caldwell, Colleen C.
Kaplan, Joshua A.
Perera, Rajika L.
Spies, Maria
Antony, Edwin
Zhang, Xiaodong
A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title_full A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title_fullStr A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title_full_unstemmed A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title_short A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA
title_sort structural and dynamic model for the assembly of replication protein a on single-stranded dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303327/
https://www.ncbi.nlm.nih.gov/pubmed/30575763
http://dx.doi.org/10.1038/s41467-018-07883-7
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