Abstract

Our DNA is the manual of instructions that cells employ to grow, divide, and even to die. This information must be faithfully passed on, generation after generation, but it is continually threatened by radiation, chemicals, and our own diet. Cells have developed clever defence mechanisms to avoid and repair DNA damage. However, these mechanisms can fail, giving rise to severe diseases. A special type of damage, called DNA crosslink, is normally repaired by our cells, but patients suffering the hereditary syndrome Fanconi Anemia (FA) fail to do so, and suffer catastrophic effects, including fatal cancers. My goal is to understand the molecular details of DNA crosslink repair, and to do so I combine biochemistry, biophysics and structural biology to visualise its underlying mechanisms at unprecedented detail. This will help us understand how this DNA damage is normally repaired and why FA patients are unable to do so.