Chemistry of Life Theme: leader of WG 1 – Structure, function and dynamics of macromolecular complexes, LINXS Fellow

Amanda Chaplin, Lecturer at the Department of Molecular and Cell Biology, University of Leicester

Dr Chaplin’s research focuses on understanding the complex mechanisms underpinning DNA-repair using cryo-electron microscopy. Specifically, her research group work on proteins involved in the non-homologous end joining (NHEJ) pathway. NHEJ is crucial for cellular survival as it functions to repair DNA double-strand breaks (DSBs), which if not repaired correctly can lead to various diseases (most notably cancer).

Dr Chaplin’s work has involved determining three-dimensional cryo-EM structures of the core proteins involved in NHEJ. Specifically, Ku70/80, DNA-PKcs, DNA-PK (the key enzyme) and supercomplexes including XLF, XRCC4 and Ligase IV. These structures have revealed the specific architecture of these elaborate complexes. They have also identified two novel dimeric forms of DNA-PK, allowing us to propose a new mechanism for NHEJ that utilises alternate oligomeric structural assemblies to respond to diverse DNA substrates.