Electron microscopy reconstructions of DNA repair complexes.

Lesions in DNA compromise the integrity of the genome; their consequences can range from cell malfunction to malignant transformation. DNA damage is repaired by huge multisubunit macromolecular complexes of dynamic composition and conformation. Hence, single-particle electron microscopy has started to contribute significantly to resolving the DNA repair machinery. In many cases, the complexity of the task means that the work requires laborious purification, well-designed strategies for image processing and meticulous labelling of subunits; often, only negative staining is feasible. Recent electron microscopy studies have revealed that the association of DNA-PKcs with Ku70/Ku80 and DNA during non-homologous end joining induces conformational changes that activate the kinase and direct the formation of a synaptic complex. Also, rearrangements of Rad51 filaments and their association with Brca2 were found to regulate homologous recombination.