Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715636
Title: A novel role for the arginine methyltransferase PRMT5 in the DNA damage response and implications for cancer therapy
Author: Clarke, Thomas Leslie
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
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Abstract:
Post-translational modifications of proteins play a critical role in the DNA damage response and in the maintenance of genome stability. However, the role of arginine methylation in these processes is poorly understood. Here, it is revealed that the arginine methyltransferase PRMT5 is a key regulator of DNA double strand break (DSB) repair through targeting RUVBL1, a critical cofactor of the Tip60 complex, for methylation at R205. RUVBL1-R205 methylation is required for Tip60-mediated H4K16 acetylation and the mobilisation of 53BP1 from DNA breaks ends, enabling DNA resection and homologous recombination repair of DSBs. Interestingly, RUVBL1 methylation is not required for Tip60-mediated ATM activation, demonstrating that PRMT5-mediated methylation of RUVBL1 is able to regulate specific activities of the Tip60 complex in response to DSBs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.715636  DOI: Not available
Keywords: QH426 Genetics ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)
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