{"id":{"repo_id":"birmingham","oai_identifier":"oai:etheses.bham.ac.uk:1129"},"canonical_url":"https://search.dev.ndltd.org/etd/birmingham/oai:etheses.bham.ac.uk:1129","repository":{"repo_id":"birmingham","name":"University of Birmingham","base_url":"https://etheses.bham.ac.uk/cgi/oai2"},"display":{"title":"The role of linker histone variant in double strand break repair","abstract":"Eukaryotic DNA is packaged into chromatin, providing a physical and structural barrier for regulatory and effector proteins to access the DNA. It has been shown that linker histone variants inhibit the double strand break (DSB) repair pathway known as non-homologous end joining (NHEJ). NHEJ, in vivo, requires the KU complex, the DNA dependent protein kinase (DNA-PK) and the DNA ligase IV/XRCC4 (LX) complex. In vitro analysis has shown that several linker histone variants are all phosphorylated by DNA-PK. Depletion of a specific linker histone variant protein levels by short interfering RNA renders cells radiosensitive and increases the levels of un-repaired DSBs following exposure to ionising radiation. This linker histone variant interacts with both DNA ligase IV and XRCC4 in vivo, along with DNA-PK, the KU complex and nucleolin. Interestingly, the interaction with nucleolin only occurs in the presence of DNA damage following exposure to ionising radiation. In vitro analysis has shown that this linker histone variant is able to form stable complexes in the presence of DNA and the LX complex, and very efficiently stimulate LX-mediated ligation of double stranded DNA. These findings establish a role for a linker histone variant in the NHEJ pathway.","abstract_html":"Eukaryotic DNA is packaged into chromatin, providing a physical and structural barrier for regulatory and effector proteins to access the DNA. It has been shown that linker histone variants inhibit the double strand break (DSB) repair pathway known as non-homologous end joining (NHEJ). NHEJ, in vivo, requires the KU complex, the DNA dependent protein kinase (DNA-PK) and the DNA ligase IV/XRCC4 (LX) complex. In vitro analysis has shown that several linker histone variants are all phosphorylated by DNA-PK. Depletion of a specific linker histone variant protein levels by short interfering RNA renders cells radiosensitive and increases the levels of un-repaired DSBs following exposure to ionising radiation. This linker histone variant interacts with both DNA ligase IV and XRCC4 in vivo, along with DNA-PK, the KU complex and nucleolin. Interestingly, the interaction with nucleolin only occurs in the presence of DNA damage following exposure to ionising radiation. In vitro analysis has shown that this linker histone variant is able to form stable complexes in the presence of DNA and the LX complex, and very efficiently stimulate LX-mediated ligation of double stranded DNA. These findings establish a role for a linker histone variant in the NHEJ pathway.","abstract_has_math":false,"creators":["Arbon, Darren D"],"institution":"University of Birmingham","degree_name":"d_ph","degree_level":"d_ph","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-12","date_published":"2010-12","updated_at":"2026-07-24T01:11:23Z","subjects":["R Medicine (General)"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["na"]},{"key":"dc:creator","label":"Author","values":["Arbon, Darren D"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-12"]},{"key":"dc:date.issued","label":"Date","values":["2010-12"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["College of Medical & Dental Sciences","School of Clinical and Experimental Medicine, Department of Medical and Molecular Genetics"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Birmingham"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["http://etheses.bham.ac.uk//id/eprint/1129/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["d_ph"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["d_ph"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["R Medicine (General)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://etheses.bham.ac.uk//id/eprint/1129/6/Arbon_10_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1129/2/Decl_IS_Arbon_10_PhD.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Eukaryotic DNA is packaged into chromatin, providing a physical and structural barrier for regulatory and effector proteins to access the DNA. It has been shown that linker histone variants inhibit the double strand break (DSB) repair pathway known as non-homologous end joining (NHEJ). NHEJ, in vivo, requires the KU complex, the DNA dependent protein kinase (DNA-PK) and the DNA ligase IV/XRCC4 (LX) complex. In vitro analysis has shown that several linker histone variants are all phosphorylated by DNA-PK. Depletion of a specific linker histone variant protein levels by short interfering RNA renders cells radiosensitive and increases the levels of un-repaired DSBs following exposure to ionising radiation. This linker histone variant interacts with both DNA ligase IV and XRCC4 in vivo, along with DNA-PK, the KU complex and nucleolin. Interestingly, the interaction with nucleolin only occurs in the presence of DNA damage following exposure to ionising radiation. In vitro analysis has shown that this linker histone variant is able to form stable complexes in the presence of DNA and the LX complex, and very efficiently stimulate LX-mediated ligation of double stranded DNA. These findings establish a role for a linker histone variant in the NHEJ pathway."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The role of linker histone variant in double strand break repair"]}]}],"canonical_facts":{"dc:contributor.sponsor":["na"],"dc:creator":["Arbon, Darren D"],"dc:date":["2010-12"],"dc:date.issued":["2010-12"],"dc:description.abstract":["Eukaryotic DNA is packaged into chromatin, providing a physical and structural barrier for regulatory and effector proteins to access the DNA. It has been shown that linker histone variants inhibit the double strand break (DSB) repair pathway known as non-homologous end joining (NHEJ). NHEJ, in vivo, requires the KU complex, the DNA dependent protein kinase (DNA-PK) and the DNA ligase IV/XRCC4 (LX) complex. In vitro analysis has shown that several linker histone variants are all phosphorylated by DNA-PK. Depletion of a specific linker histone variant protein levels by short interfering RNA renders cells radiosensitive and increases the levels of un-repaired DSBs following exposure to ionising radiation. This linker histone variant interacts with both DNA ligase IV and XRCC4 in vivo, along with DNA-PK, the KU complex and nucleolin. Interestingly, the interaction with nucleolin only occurs in the presence of DNA damage following exposure to ionising radiation. In vitro analysis has shown that this linker histone variant is able to form stable complexes in the presence of DNA and the LX complex, and very efficiently stimulate LX-mediated ligation of double stranded DNA. These findings establish a role for a linker histone variant in the NHEJ pathway."],"dc:format":["application/pdf"],"dc:identifier.uri":["http://etheses.bham.ac.uk//id/eprint/1129/6/Arbon_10_PhD.pdf","http://etheses.bham.ac.uk//id/eprint/1129/2/Decl_IS_Arbon_10_PhD.pdf"],"dc:publisher.department":["College of Medical & Dental Sciences","School of Clinical and Experimental Medicine, Department of Medical and Molecular Genetics"],"dc:publisher.institution":["University of Birmingham"],"dc:relation.isreferencedby":["http://etheses.bham.ac.uk//id/eprint/1129/"],"dc:subject":["R Medicine (General)"],"dc:title":["The role of linker histone variant in double strand break repair"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["d_ph"],"dc:type.qualificationname":["d_ph"]},"updated_at":"2026-07-24T01:11:23Z"}