DNA damaging ionizing radiation (IR) is everywhere, in the form of atmosphere-penetrating cosmic rays, environmentally prevalent radioisotopes such as radon gas and radiation-based military, medical and energy technologies. There is no biological mechanism to prevent the damage caused to cells by IR ; instead, life has evolved exquisite mechanisms to resolve it once it has formed. The most deleterious lesion caused by IR is a break in both strands of our DNA, a DNA double-strand break (DSB). Unless accurately repaired by the molecular machinery of our cells, DSBs can lead to genome instability a fundamental driver of cancer and ageing. We now know that DSBs occurring within regions of complex DNA arrangement are much more difficult to repair and require substantially more multifaceted (but as yet unclear) processes to resolve. My research endeavors to understand the molecular pathways underlying DSB repair in these regions and, in doing so, improve our knowledge of cancer formation, human ageing and radiation protection.