Regulation of small ubiquitin-like modifiers in DNA double-strand break repair

Our cells protect their DNA from long-term damage by actively repairing it. This process is vital to healthy ageing and without it cancer can arise. Cells have several rapid response mechanisms to call their internal repair services to damaged DNA. Recently we have found out that one of these mechanisms uses tiny proteins called small ubiquitin-like modifiers (SUMO). We think SUMO might act like sticky tape and it alerts repair services by sticking them to each other and to the damaged region. However, there are fundamental aspects of the way that SUMO is involved that are not understood. How does the cell initiate the ‘sticking’ processes? Too much ‘stickyness’ would be dangerous to the repair process, so how do cells stop it and what determines where they are stuck?

We aim to address how SUMO is directed to damaged DNA, how the amount of SUMO at damaged sites is controlled and whether special mechanisms exist to put it in the right place.

The regulation of SUMO is an understudied aspect of DNA repair so the knowledge we will gain is likely to provide the basis for new developments in medicine regarding cancer and healthy ageing.