Final Report Summary - DEFACT (DNA repair factories how cells do biochemistry)
The ERC starting grant to study DNA repair factories has taken a combined cell biological and genetic approach to decipher how DNA repair processes are organized in space and time in the eukaryotic cell nucleus. The spatio-temporal organization of DNA repair pathways proves to be a crucial aspect of high-fidelity genome maintenance that provides regulation and coordination with other DNA metabolic pathways. Our efforts have identified and characterized several new DNA repair factors such as Rad56, Mte1, and Cmr1. Further, we have described several aspects of DNA repair regulation by post-translational modification of DNA repair proteins by sumoylation, ubiquitylation, and acetylation, or by relocalization of the DNA lesion to a new position within the nucleus. One of the surprising findings of our work is the dynamic and continuous assembly and disassembly of DNA repair complexes during repair and the numerous novel transient protein-protein interactions mediated by post-translational modifications. The functional significance of many of these transient interactions are still being investigated, but current data indicate that the transient nature of these interaction provides both flexibility and fidelity in repair as well as a mechanism for disassembly and attenuation of DNA response complexes after repair has been completed. The project has opened new avenues of research into the contribution of additional new DNA repair factors in the coming years.