Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Biochemistry
Supervisor
Dr. Megan J. Davey
Second Advisor
Dr. Christopher J. Brandi
Third Advisor
Dr. David B. Haniford
Abstract
Genome duplication occurs once and only once during each cell cycle. It is a highly ordered process and is separated into the formation of different multi-protein complexes. The pre-replicative complex (preRC) is formed during G1 -phase and is composed of ORC, Cdc6, Cdtl and Mcm2-7. Mcm2-7 is the replicative helicase in eukaryotic cells and is assembled on replication origins prior to S-phase. Cdtl is an essential component of the preRC. Cdtl has been shown to interact with Mcm2-7, however neither the requirements nor the effects of this interaction have explored. In this study, I show that Cdtl forms a complex with Mcm2-7 without the need for other factors. Furthermore, Cdtl modulates the helicase, ATPase and DNA binding activity of the Mcm2-7 complex. I propose a model where Cdtl modulates Mcm2-7 helicase activity by inhibiting ATP hydrolysis by Mcm2-7, thus preventing premature DNA unwinding. Furthermore, the increase in dsDNA binding affinity for the Mcm2-7/Cdtl complex (Mcm2-7*Cdtl) assists in its loading onto replication origins during preRC assembly. These results indicate a novel role for Cdtl in Mcm2-7 modulation and DNA replication control.
Recommended Citation
Kolaczyk, Tomasz, "Modulation of Mcm2-7 activity by Cdtl suggests novel roles for Cdtl in the control of DNA replication" (2010). Digitized Theses. 4120.
https://ir.lib.uwo.ca/digitizedtheses/4120