Consequences and repair of radiation-induced DNA damage: fifty years of fun questions and answers

Purpose To summarize succinctly the 50 years of research undertaken in my laboratory and to provide an overview of my career in science. It is certainly a privilege to have been asked by Carmel Mothersill and Penny Jeggo to contribute to this special issue of the International Journal of Radiation Biology focusing on the work of women in the radiation sciences. Conclusion My students, post-docs and I identified and characterized a number of the enzymes that recognize and remove radiation-damaged DNA bases, the DNA glycosylases, which are the first enzymes in the Base Excision Repair (BER) pathway. Although this pathway actually evolved to repair oxidative and other endogenous DNA damages, it is also responsible for removing the vast majority of radiation-induced DNA damages including base damages, alkali-labile lesions and single strand breaks. However, because of its high efficiency, attempted BER of clustered lesions produced by ionizing radiation, can have disastrous effects on cellular DNA. We also evaluated the potential biological consequences of many of the radiation-induced DNA lesions. In addition, with collaborators, we employed computational techniques, x-ray crystallography and single molecule approaches to answer many questions at the molecular level.