Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
Identifieur interne : 000E93 ( Istex/Corpus ); précédent : 000E92; suivant : 000E94Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats
Auteurs : Samir Amrane ; Barbara Sacca ; Martin Mills ; Madhu Chauhan ; Horst H. Klump ; Jean-Louis MergnySource :
- Nucleic Acids Research [ 0305-1048 ] ; 2005.
Abstract
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.
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DOI: 10.1093/nar/gki716
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Acids Res.</title><idno type="ISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2005">2005</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="4065">4065</biblScope><biblScope unit="page" to="4077">4077</biblScope></imprint><idno type="ISSN">0305-1048</idno></series><idno type="istex">89759E7706A1C0A18331AA02611B9760B20373D6</idno><idno type="DOI">10.1093/nar/gki716</idno><idno type="local">gki716</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0305-1048</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Samir Amrane</name></json:item><json:item><name>Barbara Saccà</name></json:item><json:item><name>Martin Mills</name><affiliations><json:string>Department of Molecular and Cell Biology, University of Cape Town P.B. 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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’. 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Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org</p></availability><date>2005</date></publicationStmt><notesStmt><note>*To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: faucon@mnhn.fr</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats</title><author xml:id="author-1"><persName><forename type="first">Samir</forename><surname>Amrane</surname></persName></author><author xml:id="author-2"><persName><forename type="first">Barbara</forename><surname>Saccà</surname></persName></author><author xml:id="author-3"><persName><forename type="first">Martin</forename><surname>Mills</surname></persName><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation></author><author xml:id="author-4"><persName><forename type="first">Madhu</forename><surname>Chauhan</surname></persName><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation></author><author xml:id="author-5"><persName><forename type="first">Horst H.</forename><surname>Klump</surname></persName><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation></author><author xml:id="author-6"><persName><forename type="first">Jean-Louis</forename><surname>Mergny</surname></persName></author></analytic><monogr><title level="j">Nucleic Acids Research</title><title level="j" type="abbrev">Nucl. Acids Res.</title><idno type="pISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2005"></date><biblScope unit="volume">33</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="4065">4065</biblScope><biblScope unit="page" to="4077">4077</biblScope></imprint></monogr><idno type="istex">89759E7706A1C0A18331AA02611B9760B20373D6</idno><idno type="DOI">10.1093/nar/gki716</idno><idno type="local">gki716</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2005</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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.</p></abstract></profileDesc><revisionDesc><change when="2005">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/89759E7706A1C0A18331AA02611B9760B20373D6/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="other"><front><journal-meta><journal-id journal-id-type="hwp">nar</journal-id><journal-id journal-id-type="nlm-ta">Nucleic Acids Res</journal-id><journal-id journal-id-type="publisher-id">nar</journal-id><journal-title>Nucleic Acids Research</journal-title><abbrev-journal-title abbrev-type="publisher">Nucl. Acids Res.</abbrev-journal-title><issn pub-type="ppub">0305-1048</issn><issn pub-type="epub">1362-4962</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">gki716</article-id><article-id pub-id-type="doi">10.1093/nar/gki716</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Length-dependent energetics of (CTG)<italic><sub>n</sub></italic> and (CAG)<italic><sub>n</sub></italic> trinucleotide repeats</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Amrane</surname><given-names>Samir</given-names></name></contrib><contrib contrib-type="author"><name><surname>Saccà</surname><given-names>Barbara</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mills</surname><given-names>Martin</given-names></name><xref rid="AU1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chauhan</surname><given-names>Madhu</given-names></name><xref rid="AU1">1</xref></contrib><contrib contrib-type="author"><name><surname>Klump</surname><given-names>Horst H.</given-names></name><xref rid="AU1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mergny</surname><given-names>Jean-Louis</given-names></name><xref rid="COR1">*</xref></contrib><aff>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle USM 503 INSERM UR 565, CNRS UMR 8646, 43 rue Cuvier, 75231 Paris cedex 05, France</aff><aff id="AU1"><sup>1</sup>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</aff></contrib-group><author-notes><corresp id="COR1"><sup>*</sup>To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: <ext-link xlink:href="faucon@mnhn.fr" ext-link-type="email">faucon@mnhn.fr</ext-link></corresp></author-notes><pub-date pub-type="ppub"><year>2005</year></pub-date><volume>33</volume><issue>13</issue><fpage>4065</fpage><lpage>4077</lpage><history><date date-type="accepted"><day>30</day><month>6</month><year>2005</year></date><date date-type="received"><day>28</day><month>2</month><year>2005</year></date><date date-type="rev-recd"><day>30</day><month>6</month><year>2005</year></date></history><permissions><copyright-statement>© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact <ext-link xlink:href="journals.permissions@oupjournals.org" ext-link-type="email">journals.permissions@oupjournals.org</ext-link></copyright-statement><copyright-year>2005</copyright-year><license license-type="open-access"><p></p></license></permissions><abstract xml:lang="en"><p>Trinucleotide repeats are involved in a number of debilitating diseases such as myotonic dystrophy. Twelve to seventy-five base-long (CTG)<italic><sub>n</sub></italic> 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.</p></abstract><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>4065</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value></meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>research-article</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Length-dependent energetics of (CTG)n and (CAG)n trinucleotide repeats</title></titleInfo><name type="personal"><namePart type="given">Samir</namePart><namePart type="family">Amrane</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Barbara</namePart><namePart type="family">Saccà</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin</namePart><namePart type="family">Mills</namePart><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Madhu</namePart><namePart type="family">Chauhan</namePart><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Horst H.</namePart><namePart type="family">Klump</namePart><affiliation>Department of Molecular and Cell Biology, University of Cape Town P.B. Rondebosh 7701, Republic of South Africa</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Louis</namePart><namePart type="family">Mergny</namePart><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="other"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2005</dateIssued><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">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.</abstract><note type="author-notes">*To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: faucon@mnhn.fr</note><relatedItem type="host"><titleInfo><title>Nucleic Acids Research</title></titleInfo><titleInfo type="abbreviated"><title>Nucl. Acids Res.</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0305-1048</identifier><identifier type="eISSN">1362-4962</identifier><identifier type="PublisherID">nar</identifier><identifier type="PublisherID-hwp">nar</identifier><identifier type="PublisherID-nlm-ta">Nucleic Acids Res</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>33</number></detail><detail type="issue"><caption>no.</caption><number>13</number></detail><extent unit="pages"><start>4065</start><end>4077</end></extent></part></relatedItem><identifier type="istex">89759E7706A1C0A18331AA02611B9760B20373D6</identifier><identifier type="DOI">10.1093/nar/gki716</identifier><identifier type="local">gki716</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author 2005. Published by Oxford University Press. All rights reserved
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