(C2G4)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 (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C2G4)n DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt...

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Main Authors: Prince Kumar Lat, Dipankar Sen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198418&type=printable
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author Prince Kumar Lat
Dipankar Sen
author_facet Prince Kumar Lat
Dipankar Sen
author_sort Prince Kumar Lat
collection DOAJ
description Massive expansion of a DNA hexanucleotide sequence repeat (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C2G4)n DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C2G4)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.
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spelling doaj-art-8d7b7ad4216c4fa499aabaf6ae4b54f22025-08-20T03:13:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019841810.1371/journal.pone.0198418(C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.Prince Kumar LatDipankar SenMassive expansion of a DNA hexanucleotide sequence repeat (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C2G4)n DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C2G4)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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198418&type=printable
spellingShingle Prince Kumar Lat
Dipankar Sen
(C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.
PLoS ONE
title (C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.
title_full (C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.
title_fullStr (C2G4)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 (C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.
title_short (C2G4)n repeat expansion sequences from the C9orf72 gene form an unusual DNA higher-order structure in the pH range of 5-6.
title_sort c2g4 n repeat expansion sequences from the c9orf72 gene form an unusual dna higher order structure in the ph range of 5 6
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198418&type=printable
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AT dipankarsen c2g4nrepeatexpansionsequencesfromthec9orf72geneformanunusualdnahigherorderstructureinthephrangeof56