FIG 1.

Temporal regulation of mutagenesis by stress responses in E. coli mutagenic break repair. (Step 1) DNA double-strand breaks (DSBs) are generated by various processes and can then be repaired by homologous or microhomologous repair mechanisms. (Top) During homology-directed DSB repair (HR) (reviewed in references 74 and 75), ssDNA exposed at the DSB ends base pairs with complementary sequence in a sister chromosome, promoting repair DNA synthesis. (Step 2) DSBs also induce the SOS response, which transcriptionally upregulates the error-prone DNA polymerases (Pols) IV, V, and II (82); however, repair remains accurate unless another stressor induces the general stress (σ^S) response (44, 45). (Step 3) The σ^S response induces two kinds of switches to mutagenic DSB repair. In cells that are also SOS induced, the σ^S response, by unknown means, allows the use of, or persistence of errors made by, the error-prone DNA Pols in repair, causing base substitutions (45, 84) and indels (43, 44, 83, 166, 167). σ^S also downregulates mismatch repair (37–40, 88), which allows errors in DNA synthesis to persist. (Bottom) Less frequently, microhomologous MBR of a DSB occurs. It is SOS independent and requires (step 2) the σ^S response and DNA Pol I for template switching to regions containing microhomology (49, 50) (few complementary bases). The repair replication creates genome rearrangements. A duplicated chromosome segment is shown (blue arrows). Parallel lines represent base-paired DNA strands, and half arrowheads represent the 3′ DNA ends.