By Ruby Kell
Dr Bruno Vaz, from the Oxford Institute for Radiation Oncology, presented his research on the 3rd May 2018 at the University of Sheffield on a newly discovered gene thought to be involved in cancer and ageing.
The gene was identified in three teenage boys all of whom died of liver cancer. This is unusual as this form of cancer is normally only found in over 40s, and triggered as a result of heavy alcohol use. The patients all also exhibited signs of early ageing; muscle wastage, cataracts and joint pains. Suspecting a genetic link, Dr Vaz and his colleagues probed the genetic code of the patients. They identified a gene, SPARTAN (SPRTN) which was defective in all three boys.
Further studies revealed SPRTN is involved in repairing DNA damage. Specifically, it removes proteins that have become stuck to DNA that distort its helical-shape thereby creating a bulky obstacle for important DNA processes. Disruption of these processes means the integrity of the DNA code becomes unstable, and therefore can be easily changed and mutated. In healthy individuals, these protein lesions are rapidly dealt with and mutations are kept in check. However for Dr Vaz’s SPRTN-deficient patients, mutations can build up leading to cancers that could be up to forty years premature.
These protein-DNA deposits arise naturally in the body but they can also be triggered by external stimuli like UV light or chemotherapeutic drugs. It is the link with chemotherapy that makes the discovery of SPRTN exciting for cancer therapy. If cancer drugs owe some of their toxicity to inducing DNA-protein links, then a second drug inhibiting the SPRTN repair pathway of these lesions could significantly improve chemotherapy potency.
Furthermore, even in the absence of chemotherapy, cancer cells are more likely to house more protein-bound DNA than normal cells. This is because of their inherent nature to divide much faster than the average cell. This means that their DNA is more likely to become tangled up in proteins that facilitate the required DNA replication for this process. Targeting cells with more protein-bound DNA using a SPRTN-inhibiting drug may therefore be a way to make cancer therapies more specific, and reduce the well-known side effects of chemotherapy.
Learn more about Dr Vaz’s research here.
About the Author
Ruby is a Molecular Biology Masters student at the University of Sheffield. Her research focuses on the effect of antibiotics and how we may be able to overcome the growing issue of antimicrobial resistance. Ruby has a particular interest in science communication and outreach, and has been volunteering with the BSA since November.