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DNA Polymerase Theta
DNA Polymerase Theta and its Potential Role in Cancer
DNA is randomly damaged on a daily basis by many factors including environmental exposure and random replicative errors. This damaged DNA can lead to genomic instability and eventually cancer. The cell copes with this damage through DNA repair pathways and our research focuses on one key member, DNA polymerase Theta (Pol θ) or POLQ. DNA polymerases synthesize new DNA by “reading” the original DNA template. Poorly functioning DNA polymerases have been shown to contribute to genetic instability by incorporating the wrong nucleic acid across from the original DNA template. Pol θ performs low fidelity repair for certain types of DNA damage. Interestingly, POLQ expression has been shown to be upregulated in several types of cancer and is associated with poor survival rates. Our goal is to biochemically study mutated DNA Polymerase θ in order to better understand its role in cancer.
Dynamic Movements of DNA Polymerase θ
DNA polymerases are complex machines that replicate and repair DNA. The process by which a DNA polymerase incorporates an incoming dNTP at the 3’ OH is thought to be accomplished by a series of steps which involve big movements of the individual domains of the DNA Polymerase. It is hypothesized that these movements are responsible for nucleotide selection and maintaining the genome. Using fluorescence resonance energy transfer systems (FRET) we can watch DNA Polymerases actively move during DNA repair events. Our goal is to use this biophysical tool to better understand how these movements affect how a DNA polymerase effectively repairs DNA.
Gel Time-Lapse 2
Polyacrylamide Gel electrophoresis for single nucleotide separation.
Credit: Miles Erickson