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Title: Exploring the roles of the C-terminal of Pol2, the catalytic subunit of DNA Polymerase ɛ, in replication and checkpoint response
Author: Sillett, Nicholas
ISNI:       0000 0004 8498 0666
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2019
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During DNA duplication, the eukaryotic replisome functionally and physically links the unwinding of the template DNA with the synthesis of the novel strand. In Saccharomyces cerevisiae, the latter task is performed by three DNA polymerases, namely Pol α and Pol δ synthesizing the lagging strand, and Pol ε the leading strand. Uniquely among the polymerases, Pol ε is also involved in origin firing and is associated with activation of the S-phase checkpoint. Pol2, its catalytic subunit, is characterized by an N-terminus that contains exonuclease and polymerase domains, and an essential C-terminus. C-terminal mutants have been shown to have a range of phenotypes, including defects in origin firing, replication, DNA damage repair and checkpoint activation. However, it is unclear if all these defects arise from its origin firing deficiency or whether the C-terminus has a multi-faceted role in the functioning and maintenance of the replisome. In the work I will present, I have observed that expression of the last 236 residues of Pol2 was sufficient to partially suppress the defects in origin firing, fork progression and checkpoint signaling inherent to a truncation mutant, pol2-11. Furthermore, I identified conserved residues essential for suppressive effects of the C-terminal fragment, possibly indicating their importance in the unique versatility of this polymerase. Finally, I observed that, independently of origin firing, Pol2 appears to play a crucial role in signaling the DNA damage checkpoint.
Supervisor: Not available Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR Microbiology