The role of the mutT gene of Escherichia coli in maintaining replication fidelity

Abstract

Spontaneous mutation levels are kept low in most organisms by a variety of error-reducing mechanisms, some of which ensure a high level of fidelity during DNA replication. The mutT gene of Escherichia coli is an important participant in avoiding such replication mistakes. An inactive mutT allele is a strong mutator with strict mutational specificity: only A.T-->C.G transversions are enhanced. The biological role of the MutT protein is thought to be the prevention of A.G mispairs during replication, specifically the mispair involving a template A and an oxidized form of guanine, 8-oxoguanine, which results when the oxidized form of dGTP, 8-oxodGTP, is available as a polymerase substrate. MutT is part of an elaborate defense system that protects against the mutagenic effects of oxidized guanine as a part of substrate dGTP and chromosomal DNA. The A.G mispairings prevented by MutT are not well-recognized and/or repaired by other fidelity mechanisms such as proofreading and mismatch repair, accounting in part for the high mutator activity of mutT. MutT is a nucleoside triphosphatase with a preference for the syn form of dGTP, hydrolyzing it to dGMP and pyrophosphate. 8-oxodGTP is hydrolyzed 10 times faster than dGTP, making it a likely biological substrate for MutT. MutT is assumed to hydrolyze 8-oxodGTP in the nucleotide pool before it can be misincorporated. While the broad role of MutT in error avoidance seems resolved, important details that are still unclear are pointed out in this review.