Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598656
Title: Saccharomyces cerevisiae proteins Rtt109p and Esc2p : two novel regulators of genome stability
Author: Driscoll, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Abstract:
I reveal that Saccharomyces cerevisiae Rtt109p promotes genome stability and resistance to DNA-damaging agents, and that it does this by functionally cooperating with the histone chaperone Asf1p to maintain normal chromatin structure. Furthermore, I show that, as for Asf1p, Rtt109p is required for histone H3 acetylation on lysine 56 (K56) in vivo. Moreover I show that Rtt109p directly catalyzes this modification in vitro in a manner that is stimulated by Asf1p. These data establish Rtt109p as a member of a new class of histone acetyltransferases and show that its actions are critical fro cell survival in the presence of DNA damage during S phase. In the second part of this thesis, I reveal that cells deleted for Saccharomyces cerevisiae ESC2 exhibit synthetic sickness when combined with deletions of many genes involved in maintaining genomic stability. Moreover, I show that esc2Δ mutant cells exhibit increased recombination frequency and increased relocalisation of recombination repair protein Rad52p. Furthermore, I show that esc2Δ cells are hypersensitive to the DNA alkylating agent methane methylsulphonate and accumulate cruciform structures during replication after treatment with this drug. I therefore propose that Esc2p functions during S-phase to counteract formation of these pathological cruciform structures, thereby maintaining genomic stability. Taken together, the discovery of two more factors involved in maintaining genome stability suggests there may be more, as yet, undiscovered factors and provides further evidence for the complex nature of the cell mechanisms employed to promote genome stability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598656  DOI: Not available
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