Mismatch repair, molecular switches, and signal transduction.

Abstract

The foundation of molecular switches in biology is grounded in translation elongation and cellular signal transduction. In these systems, guanine nucleotidebound proteins (G proteins) produce the ON and OFF signaling states that act as gates for downstream biochemical processes. Recent studies on the human mismatch repair reaction have suggested a similar molecular switch that relies on adenine nucleotide-bound forms (A proteins) to produce an ON and OFF signaling state. In the field of signal transduction, the concept of a molecular switch is elementary whereas the biochemical processes of DNA repair appear foreign. Similarly, the field of DNA repair recognizes the complex machinery required for DNA manipulation events but regards biochemical signaling processes as essential cellular input but outside the genome juggernaut. The concept of a molecular switch as an integral step in mismatch repair should accelerate communication between these two fields toward a resolved and unified mechanism for biological signaling processes.