Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats

Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy. Twelve to seventy-five base-long (CTG)n oligodeoxynucleotides were analysed using a combination of biophysical [UV-absorbance, circular dichroism and differential scanning calorimetry (DSC)] and bioch...

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Main Authors:	Amrane, Samir, Saccà, Barbara, Mills, Martin, Chauhan, Madhu, Klump, Horst H., Mergny, Jean-Louis
Format:	Online
Language:	English
Published:	Oxford University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1179733/

id	pubmed-1179733
recordtype	oai_dc
spelling	pubmed-11797332005-07-22 Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats Amrane, Samir Saccà, Barbara Mills, Martin Chauhan, Madhu Klump, Horst H. Mergny, Jean-Louis Article Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy. Twelve to seventy-five base-long (CTG)n oligodeoxynucleotides were analysed using a combination of biophysical [UV-absorbance, circular dichroism and differential scanning calorimetry (DSC)] and biochemical methods (non-denaturing gel electrophoresis and enzymatic footprinting). All oligomers formed stable intramolecular structures under near physiological conditions with a melting temperature that was only weakly dependent on oligomer length. Thermodynamic analysis of the denaturation process by UV-melting and calorimetric experiments revealed an unprecedented length-dependent discrepancy between the enthalpy values deduced from model-dependent (UV-melting) and model-independent (calorimetry) experiments. Evidence for non-zero molar heat capacity changes was also derived from the analysis of the Arrhenius plots and DSC profiles. Such behaviour is analysed in the framework of an intramolecular ‘branched-hairpin’ model, in which long CTG oligomers do not fold into a simple long hairpin–stem intramolecular structure, but allow the formation of several independent folding units of unequal stability. We demonstrate that, for sequences ranging from 12 to 25 CTG repeats, an intramolecular structure with two loops is formed which we will call ‘bis-hairpin’. Similar results were also found for CAG oligomers, suggesting that this observation may be extended to various trinucleotide repeats-containing sequences. Oxford University Press 2005 2005-07-21 /pmc/articles/PMC1179733/ /pubmed/16040598 http://dx.doi.org/10.1093/nar/gki716 Text en © The Author 2005. Published by Oxford University Press. All rights reserved
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Amrane, Samir Saccà, Barbara Mills, Martin Chauhan, Madhu Klump, Horst H. Mergny, Jean-Louis
spellingShingle	Amrane, Samir Saccà, Barbara Mills, Martin Chauhan, Madhu Klump, Horst H. Mergny, Jean-Louis Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
author_facet	Amrane, Samir Saccà, Barbara Mills, Martin Chauhan, Madhu Klump, Horst H. Mergny, Jean-Louis
author_sort	Amrane, Samir
title	Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
title_short	Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
title_full	Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
title_fullStr	Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
title_full_unstemmed	Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
title_sort	length-dependent energetics of (ctg)n and (cag)n trinucleotide repeats
description	Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy. Twelve to seventy-five base-long (CTG)n oligodeoxynucleotides were analysed using a combination of biophysical [UV-absorbance, circular dichroism and differential scanning calorimetry (DSC)] and biochemical methods (non-denaturing gel electrophoresis and enzymatic footprinting). All oligomers formed stable intramolecular structures under near physiological conditions with a melting temperature that was only weakly dependent on oligomer length. Thermodynamic analysis of the denaturation process by UV-melting and calorimetric experiments revealed an unprecedented length-dependent discrepancy between the enthalpy values deduced from model-dependent (UV-melting) and model-independent (calorimetry) experiments. Evidence for non-zero molar heat capacity changes was also derived from the analysis of the Arrhenius plots and DSC profiles. Such behaviour is analysed in the framework of an intramolecular ‘branched-hairpin’ model, in which long CTG oligomers do not fold into a simple long hairpin–stem intramolecular structure, but allow the formation of several independent folding units of unequal stability. We demonstrate that, for sequences ranging from 12 to 25 CTG repeats, an intramolecular structure with two loops is formed which we will call ‘bis-hairpin’. Similar results were also found for CAG oligomers, suggesting that this observation may be extended to various trinucleotide repeats-containing sequences.
publisher	Oxford University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1179733/
_version_	1611375947509923840

Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats

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