{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80024"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80024","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Comparison of p53 Response to DNA and Chromatin Damage","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Rajan, Priyanka"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gurova, Katerina","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-30T15:11:55Z","date_published":"2019-07-30T15:11:55Z","updated_at":"2026-07-27T19:05:23Z","subjects":["oncology","molecular biology","cancer sciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/80024","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gurova, Katerina","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Rajan, Priyanka"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:11:55Z","2019","2019-05-17 14:01:36"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["oncology","molecular biology","cancer sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/80024"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","The ability of p53 to sense changes to the epigenetic program of the cell is under study. Recent research has shown that, drugs that cause epigenetic modifications are more effective in p53 deficient tumor types. Another study has shown that it is easier to induce pluripotency in cells with inactive p53. While p53 response to DNA perturbations is well classified, how it detects and responds to changes in epigenetic states is not known. Epigenetic modifications are embedded in DNA and histones, which exist in the form of chromatin. This study investigates how p53 responds to perturbations in chromatin structure and stability, while also comparing its response to DNA damage. Destabilization of chromatin, was induced by using a small molecule, anti-cancer agent called Curaxin. Curaxins are DNA intercalators that detach negatively charged DNA from positively charged histones by reducing the flexibility, overall negative charge and lengthening the DNA molecule. This leads to disassembly of nucleosomes, but has not been found to cause damage to DNA. This phenomenon, named chromatin damage, has been found to be a potent activator of p53. Bleomycin, a standard anti-cancer agent was used to induce DNA damage. The ability of the two agents to induce DNA damage was evaluated by probing for yH2AX in cell lysates and by comet assay. The ability to induce chromatin damage was evaluated by assaying for trapping of histone chaperone, FACT in the chromatin. Stabilization of p53 at various doses of lead curaxin molecule CBL0137, was compared with that of bleomycin by immunoblotting. Activity of p53 under CBL0137 and bleomycin treatment was examined by luciferase reporter assay. Changes at the level of transcriptome of the cell under the two treatment conditions was evaluated by nascent RNA isolation and sequencing. This study provided basis for understanding of a less studied role for p53- guarding the integrity of chromatin.Keywords: p53, chromatin damage, curaxins, DNA damage, anti-cancer agents.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Comparison of p53 Response to DNA and Chromatin Damage"]}]}],"canonical_facts":{"dc:contributor":["Gurova, Katerina","Roswell Park"],"dc:creator":["Rajan, Priyanka"],"dc:date":["2019-07-30T15:11:55Z","2019","2019-05-17 14:01:36"],"dc:description":["M.S.","The ability of p53 to sense changes to the epigenetic program of the cell is under study. Recent research has shown that, drugs that cause epigenetic modifications are more effective in p53 deficient tumor types. Another study has shown that it is easier to induce pluripotency in cells with inactive p53. While p53 response to DNA perturbations is well classified, how it detects and responds to changes in epigenetic states is not known. Epigenetic modifications are embedded in DNA and histones, which exist in the form of chromatin. This study investigates how p53 responds to perturbations in chromatin structure and stability, while also comparing its response to DNA damage. Destabilization of chromatin, was induced by using a small molecule, anti-cancer agent called Curaxin. Curaxins are DNA intercalators that detach negatively charged DNA from positively charged histones by reducing the flexibility, overall negative charge and lengthening the DNA molecule. This leads to disassembly of nucleosomes, but has not been found to cause damage to DNA. This phenomenon, named chromatin damage, has been found to be a potent activator of p53. Bleomycin, a standard anti-cancer agent was used to induce DNA damage. The ability of the two agents to induce DNA damage was evaluated by probing for yH2AX in cell lysates and by comet assay. The ability to induce chromatin damage was evaluated by assaying for trapping of histone chaperone, FACT in the chromatin. Stabilization of p53 at various doses of lead curaxin molecule CBL0137, was compared with that of bleomycin by immunoblotting. Activity of p53 under CBL0137 and bleomycin treatment was examined by luciferase reporter assay. Changes at the level of transcriptome of the cell under the two treatment conditions was evaluated by nascent RNA isolation and sequencing. This study provided basis for understanding of a less studied role for p53- guarding the integrity of chromatin.Keywords: p53, chromatin damage, curaxins, DNA damage, anti-cancer agents.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80024"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["oncology","molecular biology","cancer sciences"],"dc:title":["Comparison of p53 Response to DNA and Chromatin Damage"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-27T19:05:23Z"}