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Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability
Topoisomerase 1, an enzyme that relieves superhelical tension, is implicated in transcription-associated mutagenesis and genome instability-associated with neurodegenerative diseases as well as activation-induced cytidine deaminase. From proteomic analysis of TOP1-associated proteins, we identify SM...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742980/ https://www.ncbi.nlm.nih.gov/pubmed/26842758 http://dx.doi.org/10.1038/ncomms10549 |
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author | Husain, Afzal Begum, Nasim A. Taniguchi, Takako Taniguchi, Hisaaki Kobayashi, Maki Honjo, Tasuku |
author_facet | Husain, Afzal Begum, Nasim A. Taniguchi, Takako Taniguchi, Hisaaki Kobayashi, Maki Honjo, Tasuku |
author_sort | Husain, Afzal |
collection | PubMed |
description | Topoisomerase 1, an enzyme that relieves superhelical tension, is implicated in transcription-associated mutagenesis and genome instability-associated with neurodegenerative diseases as well as activation-induced cytidine deaminase. From proteomic analysis of TOP1-associated proteins, we identify SMARCA4, an ATP-dependent chromatin remodeller; FACT, a histone chaperone; and H3K4me3, a transcriptionally active chromatin marker. Here we show that SMARCA4 knockdown in a B-cell line decreases TOP1 recruitment to chromatin, and leads to increases in Igh/c-Myc chromosomal translocations, variable and switch region mutations and negative superhelicity, all of which are also observed in response to TOP1 knockdown. In contrast, FACT knockdown inhibits association of TOP1 with H3K4me3, and severely reduces DNA cleavage and Igh/c-Myc translocations, without significant effect on TOP1 recruitment to chromatin. We thus propose that SMARCA4 is involved in the TOP1 recruitment to general chromatin, whereas FACT is required for TOP1 binding to H3K4me3 at non-B DNA containing chromatin for the site-specific cleavage. |
format | Online Article Text |
id | pubmed-4742980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47429802016-03-04 Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability Husain, Afzal Begum, Nasim A. Taniguchi, Takako Taniguchi, Hisaaki Kobayashi, Maki Honjo, Tasuku Nat Commun Article Topoisomerase 1, an enzyme that relieves superhelical tension, is implicated in transcription-associated mutagenesis and genome instability-associated with neurodegenerative diseases as well as activation-induced cytidine deaminase. From proteomic analysis of TOP1-associated proteins, we identify SMARCA4, an ATP-dependent chromatin remodeller; FACT, a histone chaperone; and H3K4me3, a transcriptionally active chromatin marker. Here we show that SMARCA4 knockdown in a B-cell line decreases TOP1 recruitment to chromatin, and leads to increases in Igh/c-Myc chromosomal translocations, variable and switch region mutations and negative superhelicity, all of which are also observed in response to TOP1 knockdown. In contrast, FACT knockdown inhibits association of TOP1 with H3K4me3, and severely reduces DNA cleavage and Igh/c-Myc translocations, without significant effect on TOP1 recruitment to chromatin. We thus propose that SMARCA4 is involved in the TOP1 recruitment to general chromatin, whereas FACT is required for TOP1 binding to H3K4me3 at non-B DNA containing chromatin for the site-specific cleavage. Nature Publishing Group 2016-02-04 /pmc/articles/PMC4742980/ /pubmed/26842758 http://dx.doi.org/10.1038/ncomms10549 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 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 Husain, Afzal Begum, Nasim A. Taniguchi, Takako Taniguchi, Hisaaki Kobayashi, Maki Honjo, Tasuku Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title | Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title_full | Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title_fullStr | Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title_full_unstemmed | Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title_short | Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
title_sort | chromatin remodeller smarca4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742980/ https://www.ncbi.nlm.nih.gov/pubmed/26842758 http://dx.doi.org/10.1038/ncomms10549 |
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