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Title: Characterisation of chromosomally-localised protein phosphatase type 1 regulatory subunits in Drosophila melanogaster
Author: Glenday, Peter Sephton
ISNI:       0000 0004 2738 8113
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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PP1 is a member of the PPP family of serine/threonine phosphatases and has been found in all eukaryotic cells examined to date. The catalytic subunit of PP1 (PP1 c) has been shown to dephosphorylate a wide range of substrates in vitro but its specificity in vivo is determined by a number of regulatory subunits (R-subunits). In Drosophila PP1 c is found to be widely distributed at many discrete sites on third instar polytene chromosomes. These sites primarily overlap with actively transcribing regions, suggesting that PP1 c may regulate chromatin- associated functions, including structure, packaging and transcription. This thesis describes my investigation into the role of nuclear PP1c and a potential regulatory subunit, Protein Phosphatase Type 1 Nuclear Targeting Subunit (PNUTSDm) and the development of a new technique that allows clonal analysis of chromosome spreads from third instar salivary glands. I found that PP1c localises with PNUTSDm isoforms (PNUTSDm-L and PNUTSDm-S) at multiple sites corresponding to actively transcribing chromatin but demonstrate isoform- specific differences. The isoforms were shown to localise to chromatin through different mechanisms with localisation of PNUTSDm-L dependent on RNA or single-stranded DNA- binding. PP1 and PNUTSDm were shown to genetically interact in vivo and mutational \ analysis showed that PP1c and PNUTSDm regulate levels of phospho-histone H3 and phosphorylation of the carboxy-terminal domain of RNAPII during interphase. PNUTSDm- PP1c binding was shown to be necessary for this activity. PP1 c and PNUTSDm mutants were shown to antagonise the function of the histone H3 interphase protein kinase, Jil-1, in a range of developmental processes, and to restore H3Ser10 phosphorylation in JiI-1 mutant oocytes. The results suggest that PP1 may be the first identified interphase histone H3Ser10 phosphatase in Drosophila and that PNUTDm is the regulatory subunit required for this function.
Supervisor: Wakefield, James Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available