Much of spontaneous mutagenesis in Escherichia coli is due to error-prone DNA repair: implications for spontaneous carcinogenesis.
The role of DNA repair genes (uvrA, uvrB, uvrD, recA, recB, lexA, and umuC) in spontaneous mutation rate per bacterium per cell division (micro) was determined for the reversion of UAA (his-4 and trpE65), UAG (lacZ53), and frameshift (trpE9777) mutations, and for the occurrence of forward mutations to valine resistance. Rich growth medium enhanced micro in a wildtype strain but not in a uvrB5 strain. In minimal growth medium, the uvrA and uvrB strains had the largest micro (1.9-6.2-fold greater than that for isogenic wild-type strains, depending on the mutation assay). The uvrB strains carrying lexA, recA, umuC, or both the uvrD and rec B mutations (in combination), i.e., mutations that inhibit error-prone DNA repair, had the lowest micro values (approximately 10-fold less than the uvrB strain). Teh recA and lexA mutations also reduced micro (by approximately 2-fold) in uvr+ strains. The genetic control of the error prone repair-dependent sector of spontaneous mutagenesis was shown to be qualitatively similar to the genetic control for u.v. radiation mutagenesis. The umuC mutation, which drastically reduced spontaneous mutagensis, had no effect on genetic recombination. It is proposed that the low level of spontaneous mutagenesis observed in the recA, lexA, umuC, and the uvrD recB strains is due to errors made during DNA replication, while the enhanced level of spontaneous mutagenesis observed in the wild type, and especially in the uvrA and uvrB strains, is due to excisable lesions that are produced in the DNA by normal metabolic reactions, and that such unexcised lesions induce mutations via error-prone DNA repair. These results are discussed in terms of their relevance to spontaneous carcinogenesis.
D003470:Culture Media; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics* / Q000528:radiation effects; D005838:Genotype; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011995:Recombination, Genetic; D014466:Ultraviolet Rays
D003470:Culture Media