Converting a DNA damage checkpoint effector (UmuD(2)C) into a lesion bypass polymerase (UmuD ' C-2)

During the SOS response of Escherichia coli to DNA damage, the umuDC operon is induced, producing the trimeric protein complexes UmuD(2)C, a DNA damag e checkpoint effector, and UmuD'C-2 (DNA polymerase V), which carries out t ranslesion synthesis, the basis of 'SOS mutagenesis'. UmuD'(2), the homodim eric component of DNA pol V, is produced from UmuD by RecA-facilitated self -cleavage, which removes the 24 N-terminal residues of UmuD. We report the solution structure of UmuD'(2) (PDB ID 1I4V) and interactions within UmuD'- UmuD, a heterodimer inactive in translesion synthesis. The overall shape of UmuD'(2) in solution differs substantially from the previously reported cr ystal structure, even though the topologies of the two structures are quite similar. Most significantly, the active site residues S60 and K97 do not p oint directly at one another in solution as they do in the crystal, suggest ing that self-cleavage of UmuD might require RecA to assemble the active si te. Structural differences between UmuD'(2) and UmuD'-UmuD suggest that Umu D(2)C and UmuD(2)C might achieve their different biological activities thro ugh distinct interactions with RecA and DNA pol III.