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Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus
Adenine frequently pairs with the Hoogsteen edge of an oxidized guanine base (8OG) causing G to T transversions. The (syn)8OG:dA base pair is indistinguishable from the cognant base pair and can be extended by DNA polymerases with reduced efficiency. To examine the structural basis of this reduced e...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334213/ https://www.ncbi.nlm.nih.gov/pubmed/32620932 http://dx.doi.org/10.1038/s42003-020-1080-4 |
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author | Batra, Vinod K. Wilson, Samuel H. |
author_facet | Batra, Vinod K. Wilson, Samuel H. |
author_sort | Batra, Vinod K. |
collection | PubMed |
description | Adenine frequently pairs with the Hoogsteen edge of an oxidized guanine base (8OG) causing G to T transversions. The (syn)8OG:dA base pair is indistinguishable from the cognant base pair and can be extended by DNA polymerases with reduced efficiency. To examine the structural basis of this reduced efficiency, we sought to obtain the structure of the “product” complex of DNA polymerase (pol) β with the (syn)8OG:dA base pair at the primer terminus by soaking the binary complex crystals with a hydrolysable dCTP analogue complementary to the template base G. Crystallographic refinement of the structure revealed that the adenine of the (syn)8OG:dA base pair had been expelled from the primer terminus and a dCMP was inserted opposite 8OG in a reverse orientation; another uninserted molecule of the analogue was bound to the templating base G. This leads to an abortive complex that could form the basis of oxidatively-induced pol β stalling. |
format | Online Article Text |
id | pubmed-7334213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73342132020-07-09 Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus Batra, Vinod K. Wilson, Samuel H. Commun Biol Article Adenine frequently pairs with the Hoogsteen edge of an oxidized guanine base (8OG) causing G to T transversions. The (syn)8OG:dA base pair is indistinguishable from the cognant base pair and can be extended by DNA polymerases with reduced efficiency. To examine the structural basis of this reduced efficiency, we sought to obtain the structure of the “product” complex of DNA polymerase (pol) β with the (syn)8OG:dA base pair at the primer terminus by soaking the binary complex crystals with a hydrolysable dCTP analogue complementary to the template base G. Crystallographic refinement of the structure revealed that the adenine of the (syn)8OG:dA base pair had been expelled from the primer terminus and a dCMP was inserted opposite 8OG in a reverse orientation; another uninserted molecule of the analogue was bound to the templating base G. This leads to an abortive complex that could form the basis of oxidatively-induced pol β stalling. Nature Publishing Group UK 2020-07-03 /pmc/articles/PMC7334213/ /pubmed/32620932 http://dx.doi.org/10.1038/s42003-020-1080-4 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020 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 Batra, Vinod K. Wilson, Samuel H. Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title | Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title_full | Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title_fullStr | Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title_full_unstemmed | Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title_short | Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus |
title_sort | structure of a dna polymerase abortive complex with the 8og:da base pair at the primer terminus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334213/ https://www.ncbi.nlm.nih.gov/pubmed/32620932 http://dx.doi.org/10.1038/s42003-020-1080-4 |
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