{"id":{"repo_id":"loma-linda","oai_identifier":"oai:scholarsrepository.llu.edu:etd-1103"},"canonical_url":"https://search.dev.ndltd.org/etd/loma-linda/oai:scholarsrepository.llu.edu:etd-1103","repository":{"repo_id":"loma-linda","name":"Loma Linda University","base_url":"https://scholarsrepository.llu.edu/do/oai/"},"display":{"title":"The Impact of Nucleoside Sugar Modification on Biochemical DNA Transactions","abstract":"Discrimination by DNA polymerases controls the fidelity of DNA replication, and reduced fidelity results in mutations essential in the etiology of cancer. Polymerase discrimination operates at both dNTP insertion and subsequent elongation steps, and involves several energetic and structural factors that are as yet incompletely understood. While base pairing interactions have been studied extensively, substantially less is known about the role of sugar structure and conformation for polymerase incorporation and extension. In these studies we examined, systematically, the role of sugar structure and conformation on polymerase selection of the dNTP for insertion and polymerase elongation. To accomplish these goals, we have developed methods for the synthesis of oligonucleotides with nucleoside analogues with biased sugar conformations at the 3'-end (growing end) as well as at internucleotide positions. Through a series of thermodynamic, structural and functional studies, we reveal how sugar structure and conformational properties impact polymerase incorporation and extension behavior. The analogues proposed for this study allow an examination of structural and conformational properties, but also, this group of analogues comprises an important class of cytotoxic, antitumor and antiviral agents. The results of these studies will likely provide a clearer understanding of the role of sugar conformation in the fidelity of DNA synthesis and replication as well as reveal important insights into the activity and toxicity of several nucleoside analogues and allow prediction of the biological properties of future analogues.","abstract_html":"Discrimination by DNA polymerases controls the fidelity of DNA replication, and reduced fidelity results in mutations essential in the etiology of cancer. Polymerase discrimination operates at both dNTP insertion and subsequent elongation steps, and involves several energetic and structural factors that are as yet incompletely understood. While base pairing interactions have been studied extensively, substantially less is known about the role of sugar structure and conformation for polymerase incorporation and extension. In these studies we examined, systematically, the role of sugar structure and conformation on polymerase selection of the dNTP for insertion and polymerase elongation. To accomplish these goals, we have developed methods for the synthesis of oligonucleotides with nucleoside analogues with biased sugar conformations at the 3'-end (growing end) as well as at internucleotide positions. Through a series of thermodynamic, structural and functional studies, we reveal how sugar structure and conformational properties impact polymerase incorporation and extension behavior. The analogues proposed for this study allow an examination of structural and conformational properties, but also, this group of analogues comprises an important class of cytotoxic, antitumor and antiviral agents. The results of these studies will likely provide a clearer understanding of the role of sugar conformation in the fidelity of DNA synthesis and replication as well as reveal important insights into the activity and toxicity of several nucleoside analogues and allow prediction of the biological properties of future analogues.","abstract_has_math":false,"creators":["Williams, Adides"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Basic Sciences","degree_department":null,"school":null,"contributors":["Sowers, Lawrence C.","Buchholz, John","Duerksen-Hughes, Penelope","Neidigh, Jonathan","Zhang, Kangling"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-03-01T08:00:00Z","date_published":"2012-03-01T08:00:00Z","updated_at":"2026-07-24T02:52:15Z","subjects":["Medical Biochemistry","DNA -- Synthesis; DNA -- Biosynthesis; Glycoproteins; DNA Polymerases;","Nucleoside Sugar Modification","Biochemical DNA Transactions","DNA Replication","Polymerase Discrimination","DNA Synthesis"],"languages":["English"],"rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. 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In these studies we examined, systematically, the role of sugar structure and conformation on polymerase selection of the dNTP for insertion and polymerase elongation. To accomplish these goals, we have developed methods for the synthesis of oligonucleotides with nucleoside analogues with biased sugar conformations at the 3'-end (growing end) as well as at internucleotide positions. Through a series of thermodynamic, structural and functional studies, we reveal how sugar structure and conformational properties impact polymerase incorporation and extension behavior. The analogues proposed for this study allow an examination of structural and conformational properties, but also, this group of analogues comprises an important class of cytotoxic, antitumor and antiviral agents. The results of these studies will likely provide a clearer understanding of the role of sugar conformation in the fidelity of DNA synthesis and replication as well as reveal important insights into the activity and toxicity of several nucleoside analogues and allow prediction of the biological properties of future analogues."]},{"key":"dc:title","label":"Title","values":["The Impact of Nucleoside Sugar Modification on Biochemical DNA Transactions"]}]}],"canonical_facts":{"dc:contributor":["Sowers, Lawrence C.","Buchholz, John","Duerksen-Hughes, Penelope","Neidigh, Jonathan","Zhang, Kangling"],"dc:creator":["Williams, Adides"],"dc:description.abstract":["Discrimination by DNA polymerases controls the fidelity of DNA replication, and reduced fidelity results in mutations essential in the etiology of cancer. Polymerase discrimination operates at both dNTP insertion and subsequent elongation steps, and involves several energetic and structural factors that are as yet incompletely understood. While base pairing interactions have been studied extensively, substantially less is known about the role of sugar structure and conformation for polymerase incorporation and extension. In these studies we examined, systematically, the role of sugar structure and conformation on polymerase selection of the dNTP for insertion and polymerase elongation. To accomplish these goals, we have developed methods for the synthesis of oligonucleotides with nucleoside analogues with biased sugar conformations at the 3'-end (growing end) as well as at internucleotide positions. Through a series of thermodynamic, structural and functional studies, we reveal how sugar structure and conformational properties impact polymerase incorporation and extension behavior. The analogues proposed for this study allow an examination of structural and conformational properties, but also, this group of analogues comprises an important class of cytotoxic, antitumor and antiviral agents. The results of these studies will likely provide a clearer understanding of the role of sugar conformation in the fidelity of DNA synthesis and replication as well as reveal important insights into the activity and toxicity of several nucleoside analogues and allow prediction of the biological properties of future analogues."],"dc:identifier":["https://scholarsrepository.llu.edu/etd/104"],"dc:language":["English"],"dc:rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. 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