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Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η
DNA polymerases often incorporate non-canonical nucleotide, i.e., ribonucleoside triphosphates into the genomic DNA. Aberrant accumulation of ribonucleotides in the genome causes various cellular abnormalities. Here, we show the possible role of human nucleotide excision repair (NER) and DNA polymer...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763444/ https://www.ncbi.nlm.nih.gov/pubmed/31558768 http://dx.doi.org/10.1038/s41598-019-50421-8 |
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author | Sassa, Akira Tada, Haruto Takeishi, Ayuna Harada, Kaho Suzuki, Megumi Tsuda, Masataka Sasanuma, Hiroyuki Takeda, Shunichi Sugasawa, Kaoru Yasui, Manabu Honma, Masamitsu Ura, Kiyoe |
author_facet | Sassa, Akira Tada, Haruto Takeishi, Ayuna Harada, Kaho Suzuki, Megumi Tsuda, Masataka Sasanuma, Hiroyuki Takeda, Shunichi Sugasawa, Kaoru Yasui, Manabu Honma, Masamitsu Ura, Kiyoe |
author_sort | Sassa, Akira |
collection | PubMed |
description | DNA polymerases often incorporate non-canonical nucleotide, i.e., ribonucleoside triphosphates into the genomic DNA. Aberrant accumulation of ribonucleotides in the genome causes various cellular abnormalities. Here, we show the possible role of human nucleotide excision repair (NER) and DNA polymerase η (Pol η) in processing of a single ribonucleotide embedded into DNA. We found that the reconstituted NER system can excise the oxidized ribonucleotide on the plasmid DNA. Taken together with the evidence that Pol η accurately bypasses a ribonucleotide, i.e., riboguanosine (rG) or its oxidized derivative (8-oxo-rG) in vitro, we further assessed the mutagenic potential of the embedded ribonucleotide in human cells lacking NER or Pol η. A single rG on the supF reporter gene predominantly induced large deletion mutations. An embedded 8-oxo-rG caused base substitution mutations at the 3′-neighboring base rather than large deletions in wild-type cells. The disruption of XPA, an essential factor for NER, or Pol η leads to the increased mutant frequency of 8-oxo-rG. Furthermore, the frequency of 8-oxo-rG-mediated large deletions was increased by the loss of Pol η, but not XPA. Collectively, our results suggest that base oxidation of the embedded ribonucleotide enables processing of the ribonucleotide via alternative DNA repair and damage tolerance pathways. |
format | Online Article Text |
id | pubmed-6763444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67634442019-10-02 Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η Sassa, Akira Tada, Haruto Takeishi, Ayuna Harada, Kaho Suzuki, Megumi Tsuda, Masataka Sasanuma, Hiroyuki Takeda, Shunichi Sugasawa, Kaoru Yasui, Manabu Honma, Masamitsu Ura, Kiyoe Sci Rep Article DNA polymerases often incorporate non-canonical nucleotide, i.e., ribonucleoside triphosphates into the genomic DNA. Aberrant accumulation of ribonucleotides in the genome causes various cellular abnormalities. Here, we show the possible role of human nucleotide excision repair (NER) and DNA polymerase η (Pol η) in processing of a single ribonucleotide embedded into DNA. We found that the reconstituted NER system can excise the oxidized ribonucleotide on the plasmid DNA. Taken together with the evidence that Pol η accurately bypasses a ribonucleotide, i.e., riboguanosine (rG) or its oxidized derivative (8-oxo-rG) in vitro, we further assessed the mutagenic potential of the embedded ribonucleotide in human cells lacking NER or Pol η. A single rG on the supF reporter gene predominantly induced large deletion mutations. An embedded 8-oxo-rG caused base substitution mutations at the 3′-neighboring base rather than large deletions in wild-type cells. The disruption of XPA, an essential factor for NER, or Pol η leads to the increased mutant frequency of 8-oxo-rG. Furthermore, the frequency of 8-oxo-rG-mediated large deletions was increased by the loss of Pol η, but not XPA. Collectively, our results suggest that base oxidation of the embedded ribonucleotide enables processing of the ribonucleotide via alternative DNA repair and damage tolerance pathways. Nature Publishing Group UK 2019-09-26 /pmc/articles/PMC6763444/ /pubmed/31558768 http://dx.doi.org/10.1038/s41598-019-50421-8 Text en © The Author(s) 2019 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 Sassa, Akira Tada, Haruto Takeishi, Ayuna Harada, Kaho Suzuki, Megumi Tsuda, Masataka Sasanuma, Hiroyuki Takeda, Shunichi Sugasawa, Kaoru Yasui, Manabu Honma, Masamitsu Ura, Kiyoe Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title | Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title_full | Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title_fullStr | Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title_full_unstemmed | Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title_short | Processing of a single ribonucleotide embedded into DNA by human nucleotide excision repair and DNA polymerase η |
title_sort | processing of a single ribonucleotide embedded into dna by human nucleotide excision repair and dna polymerase η |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763444/ https://www.ncbi.nlm.nih.gov/pubmed/31558768 http://dx.doi.org/10.1038/s41598-019-50421-8 |
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