The work described in this thesis uses the fission yeast <i>Schizosaccharomyces pombe</i> as model system to analyse the molecular processes that control passage through the G<SUB>1</SUB> and S-phases of the cell-cycle. In particular, the work analyses the control of expression of <i>cdc22</i><SUP>+</SUP>, a gene whose transcript varies in abundance during the cell cycle with a maximum at the G<SUB>1</SUB>-S phase boundary. Chapter two describes the sequencing of <i>cdc22</i><SUP>+</SUP> and shows it encodes the large subunit of ribonucleotide reductase, an enzyme required for DNA precursor metabolism. In the next Chapter, <i>cis</i>-acting elements, resembling MCBs previously identified in budding yeast, are shown to be present 5' to the <i>cdc22</i><SUP>+</SUP> open reading frame. MCBs can confer cell cycle expression on a heterologous gene in fission yeast, implicating them in controlling periodic expression of <i>cdc22</i><SUP>+</SUP>. A <i>trans</i>-acting complex that specifically binds MCBs is identified, and called DSP1-for b DNA b synthesis control in <i>S.b pombe</i>. DSP1is related to DSC1, an MCB binding activity identified in budding yeast. Experiments in Chapter 3 demonstrate that the gene product of the <i>cdc10</i><SUP></SUP>+ START gene, p87<SUP>cdc10</SUP>, isa component of DSP1. Furthermore, <i>cdc22</i><SUP>+</SUP> is shown to be constitutively over-expressed in a <i>cdc10</i> mutant, <i>cdc10-C4</i>. Over-expression of <i>cdc22</i><SUP>+</SUP> in <i>cdc10-C4</i> is recessive to wild-type. It is proposed that DSP1 containing p87<SUP>cdc10-C4</SUP> is hyperactive and deregulated as a transcription complex. In summary, p87<SUP>cdc10</SUP> is part of a transcription complex that controls expression of <i>cdc22</i><SUP>+</SUP>, agene required for DNA synthesis. Thus this work demonstrates a molecular link between START and S-phase.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666255 |
| Date | January 1992 |
| Creators | McInerny, Christopher |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12615 |
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