RAD51 Protein ATP Cap Regulates Nucleoprotein Filament Stability release_vgi2cml37vfoxoayi4lgpfp62u

by Ravindra Amunugama, Robert A. Forties, Yujiong He, Kang Sup Shim, Smaranda Willcox, Yu Luo, Richard Fishel, Jack Griffith, Ralf Bundschuh

Published by The University of North Carolina at Chapel Hill University Libraries.



RAD51 mediates homologous recombination by forming an active DNA nucleoprotein filament (NPF). A conserved aspartate that forms a salt bridge with the ATP γ-phosphate is found at the nucleotide-binding interface between RAD51 subunits of the NPF known as the ATP cap. The salt bridge accounts for the nonphysiological cation(s) required to fully activate the RAD51 NPF. In contrast, RecA homologs and most RAD51 paralogs contain a conserved lysine at the analogous structural position. We demonstrate that substitution of human RAD51(Asp-316) with lysine (HsRAD51(D316K)) decreases NPF turnover and facilitates considerably improved recombinase functions. Structural analysis shows that archaebacterial Methanococcus voltae RadA(D302K) (MvRAD51(D302K)) and HsRAD51(D316K) form extended active NPFs without salt. These studies suggest that the HsRAD51(Asp-316) salt bridge may function as a conformational sensor that enhances turnover at the expense of recombinase activity.
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