A high-definition peek into the mechanics of DNA repair
The 'Dynamic single-molecule approach to DNA homologous recombination' (Dynasing) project studied the mechanisms and biological function of homologous recombination. This is the intricate exchange of sequences between homologous deoxyribonucleic acid (DNA) molecules, and is essential for genome duplication, DNA damage repair and chromosome segregation. The project's main objectives were to analyse the dynamics behind DNA strand exchange and protein assembly/disassembly, so as to better understand how homologous recombination in the form of double-strand break (DSB) repair is restricted to appropriate locations. Single molecule analysis can provide information on what is happening at this level, as well as on differences in the function and structure of these molecules. This is important in learning more about the proteins involved in this recombination process and how their DNA substrates form or become deformed. Dynasing used a combination of methods including scanning force, fluorescent microscopy and imaging techniques to conduct their investigations of DNA-bound proteins and molecular dynamics at never-before-seen resolutions. This multi-approach will pave the way for development of new tools to further examine complex protein assemblies. On the strength of such breakthroughs, researchers have been able to show that the RAD50/MRE11/NBS1 (RMN) protein complex plays a vital role in the repair of DSBs through homologous recombination. Other project successes include analysing the movement of human RAD54 protein with nanometre and millisecond resolution.
