Hewitt, Theodore (2020) MuGam homologue proteins - an analysis of function and viability as contributors to DNA repair. MSc by research thesis, University of York.
Abstract
Until recently it was thought that the only accurate DNA double strand break (DSB) repair
mechanism used by bacteria was homologous recombination (HR), recent discoveries have found
proteins that are orthologous to eukaryotic Ku heterodimeric proteins. These prokaryotic Ku
proteins like their eukaryotic counterparts function by biding non-specifically to the ends of DSBs to
recruit a DNA ligase to join the two ends of the DNA back together, this mechanism is known as nonhomologous
end joining (NHEJ). Bacteria that can utilize NHEJ to repair DNA DSBs are at a significant
advantage to those which cannot but only a select few species contain a gene for the prokaryotic Ku
protein. The protein Gam from bacteriophage Mu (MuGam) has been identified as possessing
sequence homology with the eukaryotic Ku heterodimer which has led to research into the potential
for this MuGam protein to contribute to the NHEJ repair mechanism as a functional orthologue to
the eukaryotic Ku70/80 complex. One study found that introducing MuGam to Escherichia coli K-12
MG1655 cells lead to an increase in both survival rate and instances of accurate and inaccurate
repair when the cells were subjected to a DSB inducing element. The gene for MuGam or similar
slightly mutated genes (MuGam homologues) are commonly found in many different of bacteria.
Here eight different MuGam homologues are shown to be capable of being overproduced in
Escherichia coli K-12 MG1655 that are functional in binding linear DNA using electromobility shift
assays (EMSA). The sequence similarity between MuGam and the eukaryotic Ku proteins is very low
and secondary structure predictors do not support structural similarities between the eukaryotic Ku
protein and the MuGam protein.
Metadata
Supervisors: | Christoph, Baumann |
---|---|
Awarding institution: | University of York |
Academic Units: | The University of York > Biology (York) |
Depositing User: | Mr Theodore Hewitt |
Date Deposited: | 10 May 2021 19:02 |
Last Modified: | 10 May 2021 19:02 |
Open Archives Initiative ID (OAI ID): | oai:etheses.whiterose.ac.uk:28756 |
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