Title: Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange.

Authors: Xu, Jingfei; Zhao, Lingyun; Xu, Yuanyuan; Zhao, Weixing; Sung, Patrick; Wang, Hong-Wei

Published In Nat Struct Mol Biol, (2017 Jan)

Abstract: The central step in eukaryotic homologous recombination (HR) is ATP-dependent DNA-strand exchange mediated by the Rad51 recombinase. In this process, Rad51 assembles on single-stranded DNA (ssDNA) and generates a helical filament that is able to search for and invade homologous double-stranded DNA (dsDNA), thus leading to strand separation and formation of new base pairs between the initiating ssDNA and the complementary strand within the duplex. Here, we used cryo-EM to solve the structures of human RAD51 in complex with DNA molecules, in presynaptic and postsynaptic states, at near-atomic resolution. Our structures reveal both conserved and distinct structural features of the human RAD51-DNA complexes compared with their prokaryotic counterpart. Notably, we also captured the structure of an arrested synaptic complex. Our results provide new insight into the molecular mechanisms of the DNA homology search and strand-exchange processes.

PubMed ID: 27941862

MeSH Terms: Base Sequence; Biocatalysis; Catalytic Domain; Cryoelectron Microscopy; Homologous Recombination*; Humans; Models, Molecular; Protein Conformation, alpha-Helical; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Rad51 Recombinase/chemistry; Rad51 Recombinase/ultrastructure*