{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/73080"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/73080","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Effect of oxidative stress on human telomeric DNA structural dynamics and accessibility","abstract":"The ends of human telomeric DNA consist of single-stranded overhangs of tandem TTAGGG repeats (ssTEL) that can form into a G-quadruplex (GQ). This guanine-rich sequence is prone to 8-oxoguanine (8OG) damage, which is one of the most common oxidative DNA lesions that can compromise telomere integrity. Here, we use single molecule Förster Resonance Energy Transfer (smFRET) to characterize the effect of 8OG on the structural dynamics and accessibility of ssTEL. We show that the stable GQ folding observed in ssTEL is disrupted by a single 8OG, generating dynamic conformational fluctuations of the DNA. Such structural dynamics induced by 8OG contributes to increased passive binding of complementary DNA oligonucleotides, as well as faster and more effective active binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which abolishes the Hoogsteen basepairing required for GQ folding. Our results suggest that a single 8OG can lead to destabilization of GQ folding, which may allow loading of telomeric proteins, including those involved in telomere length maintenance.","abstract_html":"The ends of human telomeric DNA consist of single-stranded overhangs of tandem TTAGGG repeats (ssTEL) that can form into a G-quadruplex (GQ). This guanine-rich sequence is prone to 8-oxoguanine (8OG) damage, which is one of the most common oxidative DNA lesions that can compromise telomere integrity. Here, we use single molecule Förster Resonance Energy Transfer (smFRET) to characterize the effect of 8OG on the structural dynamics and accessibility of ssTEL. We show that the stable GQ folding observed in ssTEL is disrupted by a single 8OG, generating dynamic conformational fluctuations of the DNA. Such structural dynamics induced by 8OG contributes to increased passive binding of complementary DNA oligonucleotides, as well as faster and more effective active binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which abolishes the Hoogsteen basepairing required for GQ folding. Our results suggest that a single 8OG can lead to destabilization of GQ folding, which may allow loading of telomeric proteins, including those involved in telomere length maintenance.","abstract_has_math":false,"creators":["Kim, Grace"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Myong, Su-A"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-21T19:59:12Z","date_published":"2015-01-21T19:59:12Z","updated_at":"2026-07-22T22:26:07Z","subjects":["Oxidative stress","8-oxo-guanine","Quadruplex","Deoxyribonucleic Acid (DNA)","Telomere","Accessibility"],"languages":["en"],"rights":["Copyright 2014 Grace Kim"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/73080","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Myong, Su-A"]},{"key":"dc:creator","label":"Author","values":["Kim, Grace"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-01-21T19:59:12Z","2017-01-22T10:15:23Z","2014-12","2015-01-21"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Bioengineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Oxidative stress","8-oxo-guanine","Quadruplex","Deoxyribonucleic Acid (DNA)","Telomere","Accessibility"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2014 Grace Kim"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/73080"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The ends of human telomeric DNA consist of single-stranded overhangs of tandem TTAGGG repeats (ssTEL) that can form into a G-quadruplex (GQ). This guanine-rich sequence is prone to 8-oxoguanine (8OG) damage, which is one of the most common oxidative DNA lesions that can compromise telomere integrity. Here, we use single molecule Förster Resonance Energy Transfer (smFRET) to characterize the effect of 8OG on the structural dynamics and accessibility of ssTEL. We show that the stable GQ folding observed in ssTEL is disrupted by a single 8OG, generating dynamic conformational fluctuations of the DNA. Such structural dynamics induced by 8OG contributes to increased passive binding of complementary DNA oligonucleotides, as well as faster and more effective active binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which abolishes the Hoogsteen basepairing required for GQ folding. Our results suggest that a single 8OG can lead to destabilization of GQ folding, which may allow loading of telomeric proteins, including those involved in telomere length maintenance.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2014-12-03T18:31:26Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Kim_Grace.pdf: 1336804 bytes, checksum: 2e051927e80370cb8183cace37136426 (MD5)","Made available in DSpace on 2015-01-21T19:59:12Z (GMT). No. of bitstreams: 1 Grace_Kim.pdf: 1336804 bytes, checksum: 2e051927e80370cb8183cace37136426 (MD5)","Embargo set by: Seth Robbins for item 73269 Lift date: 2017-01-21T19:59:39Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 73269 on 2017-01-22T10:15:23Z."]},{"key":"dc:title","label":"Title","values":["Effect of oxidative stress on human telomeric DNA structural dynamics and accessibility"]}]}],"canonical_facts":{"dc:contributor":["Myong, Su-A"],"dc:creator":["Kim, Grace"],"dc:date":["2015-01-21T19:59:12Z","2017-01-22T10:15:23Z","2014-12","2015-01-21"],"dc:description":["The ends of human telomeric DNA consist of single-stranded overhangs of tandem TTAGGG repeats (ssTEL) that can form into a G-quadruplex (GQ). This guanine-rich sequence is prone to 8-oxoguanine (8OG) damage, which is one of the most common oxidative DNA lesions that can compromise telomere integrity. Here, we use single molecule Förster Resonance Energy Transfer (smFRET) to characterize the effect of 8OG on the structural dynamics and accessibility of ssTEL. We show that the stable GQ folding observed in ssTEL is disrupted by a single 8OG, generating dynamic conformational fluctuations of the DNA. Such structural dynamics induced by 8OG contributes to increased passive binding of complementary DNA oligonucleotides, as well as faster and more effective active binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which abolishes the Hoogsteen basepairing required for GQ folding. Our results suggest that a single 8OG can lead to destabilization of GQ folding, which may allow loading of telomeric proteins, including those involved in telomere length maintenance.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2014-12-03T18:31:26Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Kim_Grace.pdf: 1336804 bytes, checksum: 2e051927e80370cb8183cace37136426 (MD5)","Made available in DSpace on 2015-01-21T19:59:12Z (GMT). No. of bitstreams: 1 Grace_Kim.pdf: 1336804 bytes, checksum: 2e051927e80370cb8183cace37136426 (MD5)","Embargo set by: Seth Robbins for item 73269 Lift date: 2017-01-21T19:59:39Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 73269 on 2017-01-22T10:15:23Z."],"dc:identifier":["http://hdl.handle.net/2142/73080"],"dc:language":["en"],"dc:rights":["Copyright 2014 Grace Kim"],"dc:subject":["Oxidative stress","8-oxo-guanine","Quadruplex","Deoxyribonucleic Acid (DNA)","Telomere","Accessibility"],"dc:title":["Effect of oxidative stress on human telomeric DNA structural dynamics and accessibility"],"dc:type":["text"],"thesis:degree_discipline":["Bioengineering"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:07Z"}