Development of New Methods for Studying DNA Thermodynamics and Structures

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dc.contributor.advisorZhang, David Yu
dc.creatorBae, Jin-hyung
dc.date.accessioned2019-05-16T19:19:47Z
dc.date.available2019-05-16T19:19:47Z
dc.date.created2019-05
dc.date.issued2019-04-23
dc.date.submittedMay 2019
dc.date.updated2019-05-16T19:19:47Z
dc.description.abstractThe thermodynamics of destabilizing DNA motifs such as bulges and mismatches are poorly characterized by melt curve analyses. I developed a new accurate and high- throughput method for measuring DNA motif thermodynamics, which I call TEEM. An experimental survey of biologically and biotechnologically relevant DNA motifs using TEEM revealed that the thermodynamic penalty of duplex destabilizing motifs are almost always temperature invariant, implying a dominant role of enthalpy. This phenomenon was remarkably general across disparate motifs such as bulges, mismatches, methylations, deaminations, and phosphorothioate backbone modifications, and directly contradicts prior DNA biophysical and biochemical models. To demonstrate the improved accuracy of structure prediction using the new thermodynamics parameters, I developed a new chemical probing method based on low-yield bisulfite conversion of cytosines. TEEM was also used to measure the stability of bulges at mononucleotide microsatellites which are clinically and forensically crucial DNA sequences. With this data and the partition function, I constructed a predictive model of the sliding bulge thermodynamics.
dc.format.mimetypeapplication/pdf
dc.identifier.citationBae, Jin-hyung. "Development of New Methods for Studying DNA Thermodynamics and Structures." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/105414">https://hdl.handle.net/1911/105414</a>.
dc.identifier.urihttps://hdl.handle.net/1911/105414
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectDNA thermodynamics
dc.subjectDNA structures
dc.titleDevelopment of New Methods for Studying DNA Thermodynamics and Structures
dc.typeThesis
dc.type.materialText
thesis.degree.departmentBioengineering
thesis.degree.disciplineEngineering
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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