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Structure of the p53/RNA polymerase II assembly

The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have...

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Autores principales: Liou, Shu-Hao, Singh, Sameer K., Singer, Robert H., Coleman, Robert A., Liu, Wei-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994806/
https://www.ncbi.nlm.nih.gov/pubmed/33767390
http://dx.doi.org/10.1038/s42003-021-01934-4
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author Liou, Shu-Hao
Singh, Sameer K.
Singer, Robert H.
Coleman, Robert A.
Liu, Wei-Li
author_facet Liou, Shu-Hao
Singh, Sameer K.
Singer, Robert H.
Coleman, Robert A.
Liu, Wei-Li
author_sort Liou, Shu-Hao
collection PubMed
description The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.
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spelling pubmed-79948062021-04-16 Structure of the p53/RNA polymerase II assembly Liou, Shu-Hao Singh, Sameer K. Singer, Robert H. Coleman, Robert A. Liu, Wei-Li Commun Biol Article The tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression. Nature Publishing Group UK 2021-03-25 /pmc/articles/PMC7994806/ /pubmed/33767390 http://dx.doi.org/10.1038/s42003-021-01934-4 Text en © The Author(s) 2021 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
Liou, Shu-Hao
Singh, Sameer K.
Singer, Robert H.
Coleman, Robert A.
Liu, Wei-Li
Structure of the p53/RNA polymerase II assembly
title Structure of the p53/RNA polymerase II assembly
title_full Structure of the p53/RNA polymerase II assembly
title_fullStr Structure of the p53/RNA polymerase II assembly
title_full_unstemmed Structure of the p53/RNA polymerase II assembly
title_short Structure of the p53/RNA polymerase II assembly
title_sort structure of the p53/rna polymerase ii assembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994806/
https://www.ncbi.nlm.nih.gov/pubmed/33767390
http://dx.doi.org/10.1038/s42003-021-01934-4
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