http://hdl.handle.net/2436/47163 Sat, 18 May 2013 16:09:56 GMT 2013-05-18T16:09:56Z http://hdl.handle.net/2436/117150 Title: Eukaryote polyphosphate kinases: is the 'Kornberg' complex ubiquitous? Authors: Hooley, Paul; Whitehead, Michael P.; Brown, Michael R. W. Abstract: Polyphosphate (poly P) is a polymer of up to several hundred phosphate residues and is important to a variety of cell processes. The main poly P synthetic enzyme in many bacteria is poly P kinase 1 (PPK1), which until recently had been detected among eukaryotes in some protists only. There is now evidence for the presence in several other eukaryotes of PPK1 homologues and also a second bacteria-type enzyme, PPK2. The latest genome databases reveal that the 'Kornberg' enzyme complex of three actin-related proteins, termed DdPPK2 in Dictyostelium discoideum, might also be ubiquitous in eukaryotes. Owing to the intimate association of poly P synthesis with the formation of structural fibres, this ubiquity indicates a central role for this molecule in the evolution of eukaryotic cells. Tue, 01 Jan 2008 00:00:00 GMT http://hdl.handle.net/2436/117150 2008-01-01T00:00:00Z http://hdl.handle.net/2436/117149 Title: Hydrophobins: new prospects for biotechnology Authors: Cox, P. W.; Hooley, Paul Abstract: Hydrophobins are small amphipathic molecules found uniquely in fungi. They perform crucial roles in allowing filamentous species to break through interfaces during aerial hyphae formation, sporulation, fruit body production and cell penetration. Initial biotechnological applications have exploited materials coated with hydrophobins to switch hydrophobic surfaces to hydrophilic and vice versa. Recent improvements in our understanding of the biophysics of hydrophobin layer formation, including the use of mixed types of molecules, together with advances in genomics promise to extend greatly the potential for hydrophobin biotechnologies. Thu, 01 Jan 2009 00:00:00 GMT http://hdl.handle.net/2436/117149 2009-01-01T00:00:00Z http://hdl.handle.net/2436/117169 Title: The Aspergillus nidulans stress response transcription factor StzA is ascomycete-specific and shows species-specific polymorphisms in the C-terminal region. Authors: Chilton, Ian J.; Delaney, C. E,; Barham-Morris, J.; Fincham, Daron A.; Hooley, Paul; Whitehead, Michael P. Abstract: Orthologues of the Aspergillus nidulans gene stzA were identified and characterised in an additional 19 fungi. These orthologues were restricted to, and found within all the Pezizomycotina subphyla of the Ascomycota, for which data are available, but not the Saccharomycotina or Taphrinomycotina subphyla. Intron analysis indicated that both intron loss and gain have occurred in this gene. The orthologous proteins demonstrate considerable size variation (between 663 and 897 amino acids); with almost all this variability accounted for by a hyper-variable region that is carboxy terminal to the zinc finger region. The Hypocrea jecorina orthologue (ACE1) has the binding site 5'AGGCA. There is evidence of competition, or interaction, between the ACE1/StzA and AreA binding sites in promoters of stzA and its orthologues, as well as genes involved in the metabolism of amino acids. The A. nidulans and A. fumigatus cpcA promoters have seven potential ACE1/StzA binding sites, six of which are highly conserved in position. Two very closely positioned sites are conserved across 14 of the 19 fungi analysed. Potential CpcA binding sites (5'TGAC/GTCA) have been identified between -50 and -170bp of the ATG start in the promoters of 16 of the stzA orthologues. Tue, 01 Jan 2008 00:00:00 GMT http://hdl.handle.net/2436/117169 2008-01-01T00:00:00Z http://hdl.handle.net/2436/117148 Title: Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line. Authors: Dibra, H. K.; Brown, J. E.; Hooley, Paul; Nicholl, I. D. Abstract: Regular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45alpha genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemo-protective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45alpha, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level. Fri, 01 Jan 2010 00:00:00 GMT http://hdl.handle.net/2436/117148 2010-01-01T00:00:00Z