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Citation

Thesis Title
Biophysical and biochemical characterisation of DNA-based inhibitors of the cytosine-mutating APOBEC3 enzymes

With the rise of anticancer drug resistance, a new approach must be taken to treat cancer. Ms Barzak investigated a particular family of enzymes which, in healthy cells, protect humans against pathogenic viruses. Usually, these enzymes restrict infection by mutating a virus鈥檚 DNA. However, in cancer cells, the mutational action of some of these enzymes, in particular the APOBEC3B (A3B), enables cancer progression, allowing cancer cells to escape the body鈥檚 immune system and develop drug resistance. Fortunately, Ms Barzak established that the action of A3B can be selectively inhibited by chemically-modified DNA molecules. She also added to our knowledge about what these enzymes look like when being inhibited: by using small-angle X-ray scattering, she obtained the first model structure of a two-domain APOBEC3 in complex with the DNA-inhibitor. The development of these DNA-based inhibitors offers a promising new approach to complement existing anticancer therapies.

Supervisors
Professor Vyacheslav Filichev
Dr Elena Harjes