Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525546
Title: The role of linker histone variant in double strand break repair
Author: Arbon, Darren D.
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2010
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.525546  DOI: Not available
Keywords: R Medicine (General)
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