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Title: Exploring the roles and mechanisms of Cdc18 in the cell cycle of fission yeast
Author: Harris, Oliver John Richard
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
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The replication factor Cdc18 (Cdc6 in other organisms) is required to initiate DNA replication and the S phase checkpoint, which restrains mitosis until replication is faithfully completed. In this thesis I have investigated these roles within the cell cycle of the single-celled eukaryote Schizosaccharomyces pombe (fission yeast), and in addition I have identified putative new roles for this replication factor. The Cdc18 ATPase loads the MCM complex, a putative DNA helicase, onto chromatin in late mitosis and early G1 phases in preparation for DNA replication. I have shown that the association of Cdc18 with chromatin does not require ATP binding, whilst ATP binding is necessary to initiate an S phase checkpoint signal. ATP binding and hydrolysis are required for MCM loading activity and hence DNA replication. I also present evidence indicating that Cdc18 can restrain mitosis from G1 in the absence of DNA replication, perhaps as part of a complex with the replication factors Cdtl and the ORC complex. From my work it appears that Cdc18 is required during S phase for at least two further roles. Firstly, Cdc18 is needed to maintain the S phase checkpoint when DNA replication is affected by perturbations that are likely to involve stalled forks or DNA damage. Secondly, Cdc18 may be required in an unperturbed S phase to prepare cells for entry into or progression through mitosis. This latter role is unlikely to involve DNA metabolism, and may instead be related to chromosome preparation or dynamics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available