Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555405
Title: Translational control of gene expression in response to DNA-damaging agents
Author: Young, Lucy A.
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2011
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Abstract:
In response to DNA damage, cells initiate a complex DNA-damage response (DDR) that includes mechanisms of DNA repair, cell cycle arrest, or in the cases of irreparable damage, apoptosis. Although regulation of the DDR has been extensively studied at the level of post-translational modifications and transcription, less is known about the role played by translational regulation. The data presented in this study describes the translational response and genome-wide translational profiles of human cells exposed to the DNA-damaging agents, ethyl methanesulphonate (EMS) and ionising radiation (IR). Exposure of HeLa cells to EMS caused a 60% decrease in global protein synthesis, mediated by phosphorylation of the a-subunit of eukaryotic initiation factor 2 (eIF2), whereas IR modulated global protein synthesis through changes in 4E-BP phosphorylation. Polysome profiling by cDNA micro array was used to identify on a genome-wide scale the differential translation of mRNAs following exposure to EMS or IR. Functional analysis of the data revealed translational regulation of distinct subsets of genes that, in the most part, were unique to EMS or IR exposure. An enrichment of genes involved in the ER stress response was identified following exposure to EMS, whereas genes involved in the mitochondrial oxidative phosphorylation pathway and ubiquitin-proteasome pathway were identified following exposure to IR. These data suggest that translation of distinct subsets of mRNAs may be necessary to initiate appropriate stress responses following exposure to different types of DNA-damaging agents, and in agreement with previous studies (powley et al., 2009) implicates translational control as an important mechanism of the DRR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.555405  DOI: Not available
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