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Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts
The mechanisms that underpin how insertions or deletions (indels) become fixed in DNA have primarily been ascribed to replication-related and/or double-strand break (DSB)-related processes. Here, we introduce a method to evaluate indels, orientating them relative to gene transcription. In so doing,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181645/ https://www.ncbi.nlm.nih.gov/pubmed/32332764 http://dx.doi.org/10.1038/s41467-020-15901-w |
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author | Georgakopoulos-Soares, Ilias Koh, Gene Momen, Sophie E. Jiricny, Josef Hemberg, Martin Nik-Zainal, Serena |
author_facet | Georgakopoulos-Soares, Ilias Koh, Gene Momen, Sophie E. Jiricny, Josef Hemberg, Martin Nik-Zainal, Serena |
author_sort | Georgakopoulos-Soares, Ilias |
collection | PubMed |
description | The mechanisms that underpin how insertions or deletions (indels) become fixed in DNA have primarily been ascribed to replication-related and/or double-strand break (DSB)-related processes. Here, we introduce a method to evaluate indels, orientating them relative to gene transcription. In so doing, we reveal a number of surprising findings: First, there is a transcriptional strand asymmetry in the distribution of mononucleotide repeat tracts in the reference human genome. Second, there is a strong transcriptional strand asymmetry of indels across 2,575 whole genome sequenced human cancers. We suggest that this is due to the activity of transcription-coupled nucleotide excision repair (TC-NER). Furthermore, TC-NER interacts with mismatch repair (MMR) under physiological conditions to produce strand bias. Finally, we show how insertions and deletions differ in their dependencies on these repair pathways. Our analytical approach reveals insights into the contribution of DNA repair towards indel mutagenesis in human cells. |
format | Online Article Text |
id | pubmed-7181645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71816452020-04-29 Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts Georgakopoulos-Soares, Ilias Koh, Gene Momen, Sophie E. Jiricny, Josef Hemberg, Martin Nik-Zainal, Serena Nat Commun Article The mechanisms that underpin how insertions or deletions (indels) become fixed in DNA have primarily been ascribed to replication-related and/or double-strand break (DSB)-related processes. Here, we introduce a method to evaluate indels, orientating them relative to gene transcription. In so doing, we reveal a number of surprising findings: First, there is a transcriptional strand asymmetry in the distribution of mononucleotide repeat tracts in the reference human genome. Second, there is a strong transcriptional strand asymmetry of indels across 2,575 whole genome sequenced human cancers. We suggest that this is due to the activity of transcription-coupled nucleotide excision repair (TC-NER). Furthermore, TC-NER interacts with mismatch repair (MMR) under physiological conditions to produce strand bias. Finally, we show how insertions and deletions differ in their dependencies on these repair pathways. Our analytical approach reveals insights into the contribution of DNA repair towards indel mutagenesis in human cells. Nature Publishing Group UK 2020-04-24 /pmc/articles/PMC7181645/ /pubmed/32332764 http://dx.doi.org/10.1038/s41467-020-15901-w Text en © The Author(s) 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 Georgakopoulos-Soares, Ilias Koh, Gene Momen, Sophie E. Jiricny, Josef Hemberg, Martin Nik-Zainal, Serena Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title | Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title_full | Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title_fullStr | Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title_full_unstemmed | Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title_short | Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
title_sort | transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181645/ https://www.ncbi.nlm.nih.gov/pubmed/32332764 http://dx.doi.org/10.1038/s41467-020-15901-w |
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