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(C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6
Massive expansion of a DNA hexanucleotide sequence repeat (C(2)G(4)) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C(2)G(4))(n) DNAs fold to form G-quadruplexes. We have found that in magnesium or lit...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005549/ https://www.ncbi.nlm.nih.gov/pubmed/29912891 http://dx.doi.org/10.1371/journal.pone.0198418 |
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author | Lat, Prince Kumar Sen, Dipankar |
author_facet | Lat, Prince Kumar Sen, Dipankar |
author_sort | Lat, Prince Kumar |
collection | PubMed |
description | Massive expansion of a DNA hexanucleotide sequence repeat (C(2)G(4)) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C(2)G(4))(n) DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C(2)G(4))(n) oligonucleotides fold to form a distinctive higher order structure whose most striking feature is an “inverted” circular dichroism spectrum, which is distinguishable from the spectrum of the left handed DNA double-helix, Z-DNA. On the basis of CD spectroscopy, gel mobility as well as chemical protection analysis, we propose that this structure, which we call “iCD-DNA”, may be a left-handed Hoogsteen base-paired duplex, an unorthodox G-quadruplex/i-motif composite, or a non-canonical, “braided” DNA triplex. Given that iCD-DNA forms under slightly acidic solution conditions, we do not know at this point in time whether or not it forms within living cells. |
format | Online Article Text |
id | pubmed-6005549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60055492018-06-25 (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 Lat, Prince Kumar Sen, Dipankar PLoS One Research Article Massive expansion of a DNA hexanucleotide sequence repeat (C(2)G(4)) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C(2)G(4))(n) DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C(2)G(4))(n) oligonucleotides fold to form a distinctive higher order structure whose most striking feature is an “inverted” circular dichroism spectrum, which is distinguishable from the spectrum of the left handed DNA double-helix, Z-DNA. On the basis of CD spectroscopy, gel mobility as well as chemical protection analysis, we propose that this structure, which we call “iCD-DNA”, may be a left-handed Hoogsteen base-paired duplex, an unorthodox G-quadruplex/i-motif composite, or a non-canonical, “braided” DNA triplex. Given that iCD-DNA forms under slightly acidic solution conditions, we do not know at this point in time whether or not it forms within living cells. Public Library of Science 2018-06-18 /pmc/articles/PMC6005549/ /pubmed/29912891 http://dx.doi.org/10.1371/journal.pone.0198418 Text en © 2018 Lat, Sen 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 use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lat, Prince Kumar Sen, Dipankar (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title_full | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title_fullStr | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title_full_unstemmed | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title_short | (C(2)G(4))(n) repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6 |
title_sort | (c(2)g(4))(n) repeat expansion sequences from the c9orf72 gene form an unusual dna higher-order structure in the ph range of 5-6 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005549/ https://www.ncbi.nlm.nih.gov/pubmed/29912891 http://dx.doi.org/10.1371/journal.pone.0198418 |
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