Fowler R G, Schaaper R M
Department of Biological Sciences, San Jose State University, CA 95192, USA.
FEMS Microbiol Rev. 1997 Aug;21(1):43-54. doi: 10.1111/j.1574-6976.1997.tb00344.x.
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.
在大多数生物体中，自发突变水平通过多种减少错误的机制保持在较低水平，其中一些机制可确保DNA复制过程中的高保真度。大肠杆菌的mutT基因是避免此类复制错误的重要参与者。无活性的mutT等位基因是一种具有严格突变特异性的强诱变剂：只有A.T→C.G颠换会增加。MutT蛋白的生物学作用被认为是在复制过程中防止A.G错配，特别是涉及模板A和鸟嘌呤氧化形式8-氧鸟嘌呤的错配，当氧化形式的dGTP（8-氧代dGTP）作为聚合酶底物时就会产生这种错配。MutT是一个精心设计的防御系统的一部分，该系统可保护细胞免受氧化鸟嘌呤作为底物dGTP和染色体DNA的诱变作用。MutT所防止的A.G错配不能被其他保真机制（如校对和错配修复）很好地识别和/或修复，这部分解释了mutT的高诱变活性。MutT是一种核苷三磷酸酶，偏好dGTP的顺式形式，将其水解为dGMP和焦磷酸。8-氧代dGTP的水解速度比dGTP快10倍，使其成为MutT可能的生物学底物。假定MutT在核苷酸池中水解8-氧代dGTP，以免其被错误掺入。虽然MutT在避免错误方面的广泛作用似乎已经明确，但本综述指出了一些仍不清楚的重要细节。
