Diamond’s Electron Bio-Imaging Facility (eBIC) has been used to generate the first 3D structure of the Fanconi anaemia (FA) core complex, a multi-subunit E3 ubiquitin ligase required for the repair of damaged DNA. The work, led by Dr Lori Passmore from the MRC Laboratory of Molecular Biology and a team of researchers, has been published today in Nature, and their research provides the molecular architecture of the FA core complex and new insights into how the complex functions.
The FA pathway senses and repairs DNA crosslinks that occur after exposure to chemicals including chemotherapeutic agents and alcohol, but also as a result of normal cellular metabolism. The megadalton FA core complex acts as an E3 ubiquitin ligase to initiate removal of these DNA crosslinks, helping to repair the damage caused. The research team used eBIC’s imaging facilities to make a major breakthrough in understanding the FA core complex by determining its structure using an integrative approach including cryo-electron microscopy and mass spectrometry.
Dr Peijun Zhang, Director of eBIC notes that:
Enabling cutting-edge research like this is exactly why we established eBIC, to provide scientists with state-of-the-art experimental equipment and expertise in the field of cryo-electron microscopy, for both single particle analysis and cryo-electron tomography. Determining the structure of the FA core complex for the first time is a fantastic achievement for the MRC research team.
Credit: Phospho Biomedical Animation