A model for SOS-lesion-targeted mutations in Escherichia coli

The UmuD'C-2 protein complex (Escherichia coli pol V)(1-3) is a low-fidelit y DNA polymerase (pol) that copies damaged DNA in the presence of RecA, sin gle-stranded-DNA binding protein (SSB) and the beta,gamma -processivity com plex of E. coli pol III (ref. 4). Here we propose a model to explain SOS-le sion-targeted mutagenesis, assigning specific biochemical functions for eac h protein during translesion synthesis. (SOS lesion-targeted mutagenesis oc curs when pol V is induced as part of the SOS response to DNA damage and in correctly incorporates nucleotides opposite template lesions.) Pol V plus S SB catalyses RecA filament disassembly in the 3' to 5' direction on the tem plate, ahead of the polymerase, in a reaction that does not involve ATP hyd rolysis. Concurrent ATP-hydrolysis-driven filament disassembly in the 5' to 3' direction results in a bidirectional stripping of RecA from the templat e strand. The bidirectional collapse of the RecA filament restricts DNA syn thesis by pol V to template sites that are proximal to the lesion, thereby minimizing the occurrence of untargeted mutations at undamaged template sit es.