Research led by the University of California, Irvine, has identified two ways in which a vital enzyme — responsible for genetic changes that lead to cancer and fighting viral infections — is controlled.The enzyme, APOBEC3A, protects cells against viral infections by inducing mutations to block viruses from replicating. But these mutations can also lead to cancer.
"In our previous studies, we demonstrated that APOBEC3A-induced DNA mutations are very frequent in cancer patients," said Rémi Buisson, PhD, an assistant professor in the UCI School of Medicine Department of Biological Chemistry. "In fact, we found they are present in up to 80% of certain cancer types such as lung, breast or bladder cancers."
In the study, published in Nature, Sunwoo Oh and Elodie Bournique, PhD from UCI School of Medicine explained how APOBEC3A stimulus is increased by viral infection and genotoxic stress caused by chemotherapeutic drugs. Their work shows how the enzyme is essential in eliminating viruses because the viral infection triggers an immune response that activates it, but the activation can also cause mutations that enhance the aggression of cancer.
"Together, our results reveal different ways for the cells to regulate APOBEC3A expression to address different types of stress that the cell may encounter," said Buisson. "By understanding how cancer cells and viral infections regulate APOBEC3A expression, we are poised to take a critical step forward toward the development of both new therapeutic strategies to fight cancer and new anti-viral therapies."
More work is needed to find a way to prevent APOBEC3A from creating mutations that enhance cancer. As for viral infections, the next stage is to see whether certain mutations found in infections such as COVID-19 result from APOBEC3A.