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Title: Mathematical models for DNA replication machinery
Author: Hameister, Heike
ISNI:       0000 0004 2726 089X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2012
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DNA replication and associated processes take place in all living organisms with the same constitutions. The knowledge of the duplication process, chromatin building and repair mechanisms has increased explosively over the last years, but the complex interplay of different proteins and their mechanisms are not conceived properly. During DNA replication, the DNA has to be unpacked, duplicated and finally repacked into chromatin. These steps require different proteins, e.g. new histone proteins on demand to secure an error-free and undelayed DNA replication. This thesis includes different mathematical models for DNA replication, repair and chromatin formation, which are based on experimental results. Three models of chromatin formation provide a simplified description of histone gene expression and protein synthesis during G1/S/G2 phase and include the contribution of different regulatory elements. Furthermore, all models present two different mechanisms of regulation to test possible scenarios of newly synthesised histones and free DNA binding sites. The basic model presents a single histone gene, which codes for a single histone protein. The stem-loop binding protein (SLBP) acts as a master regulator, which is only present during S phase. Different analyses of early S-phase, over- and underexpressed replication and the down-regulation of SLBP proof the model under extreme conditions. This basic model serves as a template for further scenarios with several genes and different histone families. For this, a second model is realised to simulate imbalances in the histone mRNA synthesis and translation. Additionally, a third model tests a gene knock-out and mRNA silencing. The initial histone model is able to qualitatively reproduce experimental observations and shows basic regulatory principles. The adaptation with several genes and different histone families presents qualitatively different system responses for the discussed regulatory mechanisms and illustrates the ability to compensate the effect of mRNA silencing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: DNA replication