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Title: Using high-throughput data to imply gene function : assessment of selected genes for roles in mitotic and meiotic DNA processing
Author: Jordan, Philip
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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A method of integrating large data sets of S. cerevisiae was developed here to select novel genes that possess characteristics implying their involvement in DNA processing. Form this method 54 genes were selected and mutants of these genes were screened for phenotype abnormalities associated with both meiotic and mitotic DNA processing. Eleven mutants were found to be sensitive to hydroxyurea (Δsoh1, Δrtt101, Δfyv6, Δhur1Δ/pmr1, Δbre5, Δmms22, Δbrel, Δvid21, Δsgf73, Δrmd11, Δdef1, and Δlgel; 20.4%) and two (Δdef1 and Δmms22; 3.7%) were found to be sensitive to methyl methanesulfonate during vegetative growth. Six mutants were found to have low levels of nuclear division during meiosis (Δbre1, Δvid21, Δsg73, Δarmd11, Δdef1, and Δlgel; 11.1%), four mutants displayed reductions in heteroallelic recombination in meiosis (Δsoh1, Δbre5, Δhda2 and Δygl250w; 7.4%) and higher levels of nondisjunction in meiosis was observed in two mutants (Δsoh1, and Δyp1107; 3.7%). Genes that were required for normal meiotic nuclear division (MND genes) were further assessed by analysing pre-meiotic DNA replication. One mutant (Δvid21) failed to initiate pre-meiotic DNA replication ; the other five mutants (Δbre1, Δsgf73, Δrmd11, Δdef1, and Δlge1)  were observed to have a delay in entry and lengthened time to complete pre-meiotic DNA replication. From cytological analysis of the MND mutants able to undergo pre-meiotic DNA replication it was shown that a Δdef1 strain homologous chromosomes associate during meiosis I but chromosome synapsis is abnormal. Finally a mutation that interrupts PMR1 was shown to over-replicate its genome during meiosis and form asci with greater then the normal four spores that are mostly inviable.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available