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Title: SUMOylation and chromatin remodelling in Drosophila melanogaster
Author: Bassett, A. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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The thesis describes the analysis of the function of the small ubiquitin-like modifier (SUMO) in Drosophila melanogaster, and a potential effector of such modification, the chromatin remodelling factor dATRX. A substrate of SUMO modification, the transcriptional repressor Tramtrack 69 was verified, and the site of SUMO modification narrowed to a single lysine residue. Mutation of this prevented SUMOylation, and the functional consequence of this was analysed in a variety of assays, including transcriptional repression, subcellular localisation, degradation and overexpression in fly tissues. The ETS-domain transcription factor Pointed was also identified as a potential SUMO substrate and the functional consequences of such a modification analysed in a similar manner. The role of SUMOylation in the intact fly was analysed through clonal loss of function and overexpression phenotypes in both adult and larval fly tissues, implicating it in wing and eye development and melanotic tumour formation. The similarities to the phenotypes of mutation in dISW1, another chromatin remodelling factor are discussed. SUMO was shown to be a strong suppressor of position effect variegation (PEV) and potential mechanisms for its action are discussed. The mechanism by which SUMOylation acts is addressed through analysis of SUMO interacting proteins using a yeast two-hybrid screen. This identified the chromatin remodelling complexes NuRD and dATRX and the histone methyltransferase pR-Set7 as potential effectors of SUMO modification, which were verified by GST-pulldown assay. They were shown to interact with wild type SUMO but not a mutant form that is unable to repress transcription, suggesting a possible role in transcriptional repression by SUMO.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available