| dc.identifier.uri | http://hdl.handle.net/11401/76503 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | 8-oxo-7,8-dihydro-2′-deoxyguanosine is a major oxidative product present in cells and can arise in either DNA (8-oxo-dG) or the nucleotide pool (8-oxo-dGTP). Both 8-oxo-dG and 8-oxo-dGTP exhibit dual-coding potential and can pair with cytosine or adenine. Accordingly, these lesions interfere with replication by DNA polymerases, lead to mutation and ultimately drive diseases such as cancer. Interestingly, DNA polymerase lambda (Pol λ) is uniquely capable of facilitating the error-free bypass of 8-oxo-dG-containing DNA and has thus been implicated in its repair. As such, I have utilized structural techniques (X-ray crystallography), complemented with biochemical experiments (steady-state kinetics), to gain insight into the mechanism of 8-oxo-dG bypass in Pol λ. Moreover, considering that Pol λ operates under conditions where oxidative damage is prevalent, it is also expected to frequently encounter 8-oxo-dGTP. Thus, I have characterized Pol λ in the context of 8-oxo-dGTP to further understand the mechanisms governing nucleotide selectivity. Together, my results provide a framework for understanding how DNA polymerases cope with oxidative DNA damage. | |
| dcterms.abstract | 8-oxo-7,8-dihydro-2′-deoxyguanosine is a major oxidative product present in cells and can arise in either DNA (8-oxo-dG) or the nucleotide pool (8-oxo-dGTP). Both 8-oxo-dG and 8-oxo-dGTP exhibit dual-coding potential and can pair with cytosine or adenine. Accordingly, these lesions interfere with replication by DNA polymerases, lead to mutation and ultimately drive diseases such as cancer. Interestingly, DNA polymerase lambda (Pol λ) is uniquely capable of facilitating the error-free bypass of 8-oxo-dG-containing DNA and has thus been implicated in its repair. As such, I have utilized structural techniques (X-ray crystallography), complemented with biochemical experiments (steady-state kinetics), to gain insight into the mechanism of 8-oxo-dG bypass in Pol λ. Moreover, considering that Pol λ operates under conditions where oxidative damage is prevalent, it is also expected to frequently encounter 8-oxo-dGTP. Thus, I have characterized Pol λ in the context of 8-oxo-dGTP to further understand the mechanisms governing nucleotide selectivity. Together, my results provide a framework for understanding how DNA polymerases cope with oxidative DNA damage. | |
| dcterms.available | 2017-09-20T16:50:29Z | |
| dcterms.contributor | Garcia-Diaz, Miguel | en_US |
| dcterms.contributor | de los Santos, Carlos | en_US |
| dcterms.contributor | Demple, Bruce | en_US |
| dcterms.contributor | Hollingsworth, Nancy. | en_US |
| dcterms.creator | Burak, Matthew John | |
| dcterms.dateAccepted | 2017-09-20T16:50:29Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:29Z | |
| dcterms.description | Department of Molecular and Cellular Pharmacology | en_US |
| dcterms.extent | 136 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76503 | |
| dcterms.issued | 2016-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:29Z (GMT). No. of bitstreams: 1
Burak_grad.sunysb_0771E_12813.pdf: 209832699 bytes, checksum: 98293834c58dff278cf27e2d1fab172a (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | 8-oxo-dG, 8-oxo-dGTP, DNA polymerase lambda, DNA repair | |
| dcterms.subject | Biology -- Chemistry | |
| dcterms.title | The role of DNA polymerase lambda in the repair of oxidative DNA damage | |
| dcterms.type | Dissertation | |
