Archaeal RadAs are close homologues of eukaryal Rad51s ( approximately 40%
sequence identities). These recombinases promote a hallmark strand exchange
process between homologous single-stranded and double-stranded DNA substrates.
This DNA-repairing function also plays a key role in cancer cells' resistance to
chemo- and radiotherapy. Inhibition of the strand exchange process may render
cancer cells more susceptible to therapeutic treatment. We found that
metatungstate is a potent inhibitor of RadA from Methanococcus voltae. The
tungsten cluster binds RadA in the axial DNA-binding groove. This polyanionic
species appears to inhibit RadA by locking the protein in its inactive
conformation.