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The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures
G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417164/ https://www.ncbi.nlm.nih.gov/pubmed/25813041 http://dx.doi.org/10.1093/nar/gkv252 |
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author | Zhou, Jia Fleming, Aaron M. Averill, April M. Burrows, Cynthia J. Wallace, Susan S. |
author_facet | Zhou, Jia Fleming, Aaron M. Averill, April M. Burrows, Cynthia J. Wallace, Susan S. |
author_sort | Zhou, Jia |
collection | PubMed |
description | G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood. Here, we show that the oxidized guanine lesions 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) reduce the thermostability and alter the folding of telomeric quadruplexes in a location-dependent manner. Also, the NEIL1 and NEIL3 DNA glycosylases can remove hydantoin lesions but none of the glycosylases, including OGG1, are able to remove 8-oxoG from telomeric quadruplexes. Interestingly, a hydantoin lesion at the site most prone to oxidation in quadruplex DNA is not efficiently removed by NEIL1 or NEIL3. However, NEIL1, NEIL2 and NEIL3 remove hydantoins from telomeric quadruplexes formed by five TTAGGG repeats much more rapidly than the commonly studied four-repeat quadruplex structures. We also show that APE1 cleaves furan in selected positions in Na(+)-coordinated telomeric quadruplexes. In promoter G-quadruplex DNA, the NEIL glycosylases primarily remove Gh from Na(+)-coordinated antiparallel quadruplexes but not K(+)-coordinated parallel quadruplexes containing VEGF or c-MYC promoter sequences. Thus, the NEIL DNA glycosylases may be involved in both telomere maintenance and in gene regulation. |
format | Online Article Text |
id | pubmed-4417164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44171642015-05-12 The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures Zhou, Jia Fleming, Aaron M. Averill, April M. Burrows, Cynthia J. Wallace, Susan S. Nucleic Acids Res Genome Integrity, Repair and Replication G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood. Here, we show that the oxidized guanine lesions 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) reduce the thermostability and alter the folding of telomeric quadruplexes in a location-dependent manner. Also, the NEIL1 and NEIL3 DNA glycosylases can remove hydantoin lesions but none of the glycosylases, including OGG1, are able to remove 8-oxoG from telomeric quadruplexes. Interestingly, a hydantoin lesion at the site most prone to oxidation in quadruplex DNA is not efficiently removed by NEIL1 or NEIL3. However, NEIL1, NEIL2 and NEIL3 remove hydantoins from telomeric quadruplexes formed by five TTAGGG repeats much more rapidly than the commonly studied four-repeat quadruplex structures. We also show that APE1 cleaves furan in selected positions in Na(+)-coordinated telomeric quadruplexes. In promoter G-quadruplex DNA, the NEIL glycosylases primarily remove Gh from Na(+)-coordinated antiparallel quadruplexes but not K(+)-coordinated parallel quadruplexes containing VEGF or c-MYC promoter sequences. Thus, the NEIL DNA glycosylases may be involved in both telomere maintenance and in gene regulation. Oxford University Press 2015-04-30 2015-03-26 /pmc/articles/PMC4417164/ /pubmed/25813041 http://dx.doi.org/10.1093/nar/gkv252 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Zhou, Jia Fleming, Aaron M. Averill, April M. Burrows, Cynthia J. Wallace, Susan S. The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title | The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title_full | The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title_fullStr | The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title_full_unstemmed | The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title_short | The NEIL glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex DNA structures |
title_sort | neil glycosylases remove oxidized guanine lesions from telomeric and promoter quadruplex dna structures |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417164/ https://www.ncbi.nlm.nih.gov/pubmed/25813041 http://dx.doi.org/10.1093/nar/gkv252 |
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