Upon starvation some Escherichia coli cells undergo a transient, genome-wid
e hypermutation (called adaptive mutation) that is recombination-dependent
and appears to be a response to a stressful environment. Adaptive mutation
may reflect an inducible mechanism that generates genetic variability in ti
mes of stress. Previously, however, the regulatory components and signal tr
ansduction pathways controlling adaptive mutation were unknown. Here we sho
w that adaptive mutation is regulated by the SOS response, a complex, grade
d response to DNA damage that includes induction of gene products blocking
cell division and promoting mutation, recombination, and DNA repair. We fin
d that SOS-induced levels of proteins other than RecA are needed for adapti
ve mutation. We report a requirement of RecF for efficient adaptive mutatio
n and provide evidence that the role of RecF in mutation is to allow SOS in
duction. We also report the discovery of an SOS-controlled inhibitor of ada
ptive mutation, PsiB. These results indicate that adaptive mutation is a ti
ghtly regulated response, controlled both positively and negatively by the
SOS system.