(A) Under normal conditions, LexA acts as a transcriptional repressor of over 40 downstream genes that mediate error-prone DNA replication and DNA repair, including uvrA, uvrB, and uvrC, which encode proteins that mediate nucleotide excision repair; umuC, and umuD, which encode subunits of the error-prone DNA polymerase V; and polB, which encodes another polymerase involved in the SOS response. (B) In the presence of DNA-damaging insults, such as UV light, the presence of single-stranded DNA triggers the formation of RecA filaments, which are important in the DNA strand–exchange reaction. RecA filaments also promote the autocatalytic cleavage of LexA, which derepresses genes involved in resolving DNA lesions. Evelyn Witkin’s work provided a key framework for understanding the SOS response and predicted the presence of error-prone polymerases.