Development of New Methods for Studying DNA Thermodynamics and Structures
| dc.contributor.advisor | Zhang, David Yu | en_US |
| dc.creator | Bae, Jin-hyung | en_US |
| dc.date.accessioned | 2019-05-16T19:19:47Z | en_US |
| dc.date.available | 2019-05-16T19:19:47Z | en_US |
| dc.date.created | 2019-05 | en_US |
| dc.date.issued | 2019-04-23 | en_US |
| dc.date.submitted | May 2019 | en_US |
| dc.date.updated | 2019-05-16T19:19:47Z | en_US |
| dc.description.abstract | The 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. | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Bae, 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>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/105414 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright 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. | en_US |
| dc.subject | DNA thermodynamics | en_US |
| dc.subject | DNA structures | en_US |
| dc.title | Development of New Methods for Studying DNA Thermodynamics and Structures | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Bioengineering | en_US |
| thesis.degree.discipline | Engineering | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |
Files
Original bundle
1 - 1 of 1