Mismatch repair is diminished during stationary-phase mutation

This paper is an invited Response to a recent Commentary [P.L. Foster, Rev. Mut. Res. 436 (1999) 179-184] entitled "Are adaptive mutations due to a de cline in mismatch repair? The evidence is lacking". The Commentary argues t hat no evidence exists supporting the idea that mismatch repair is limiting specifically during stationary-phase mutation. A primary concern of the au thor is to question the method that we used previously to measure growth-de pendent mutation. In this method, mutation rates are calculated using count s of mutant colonies taken at times when those colonies arise, rather than at a predetermined, fixed time, Here we show further data that illustrate w hy this must be done to ensure accurate mutation measurements. Such accurac y was necessary for our published determination that mismatch repair protei ns are not limiting during growth-dependent mutation, but become so during stationary-phase mutation. We review the evidence supporting the idea that stationary-phase reversion of a lac frameshift mutation occurs in an enviro nment of decreased mismatch repair capacity. Those data are substantial. Th e data presented in the Commentary, in apparent contradiction to this idea, do not justify the conclusion presented there. (C) 1999 Elsevier Science B .V. All rights reserved.