Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA

  • Pellegrini L
  • Wuite G
  • Candelli A
  • et al.
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Abstract

An essential mechanism for repairing DNA double-strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein fila-ment on single-stranded DNA, promoting DNA-strand exchange. Here, we study the interaction of hRAD51 with single-stranded DNA using a single-molecule approach. We show that ATP-bound hRAD51 filaments can exist in two different states with different contour lengths and with a free-energy difference of ~4 k B T per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly-competent ADP-bound configuration. In agreement with the single-molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51-ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51-ATP filaments can exist in two inter-convertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.

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Pellegrini, L., Wuite, G. J., Candelli, A., Modesti, M., Peterman, E. J., Brouwer, I., … Garcin, E. B. (2018). Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA. The EMBO Journal. https://doi.org/10.15252/embj.201798162

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