Spectra of Spontaneous Mutations in Escherichia coli Strains Defective in Mismatch Correction: The Nature of in vivo DNA Replication Errors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-09, Vol.84 (17), p.6220-6224
• Main Authors: Schaaper, Roel M., Dunn, Ronnie L.
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Chromosome Deletion; DNA mismatch repair; DNA Repair; DNA Replication; DNA, Bacterial - biosynthesis; DNA, Bacterial - genetics; Escherichia coli; Escherichia coli - genetics; Frameshift mutation; Fundamental and applied biological sciences. Psychology; Generally accepted auditing standards; Genetic mutation; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutation; Nonsense mutation; Nucleotide sequences; Nucleotides; rev genes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.17.6220

We have determined the DNA sequence changes in 487 spontaneous mutations in the N-terminal part of the lacI gene in mutH, mutL, and mutS strains of Escherichia coli. These strains display elevated spontaneous mutation rates because of a deficiency in the process of postreplicative mismatch correction. As a consequence the mutational spectra reveal the nature of spontaneous DNA replication errors. The spectra consist of base substitutions (75%) and single-base deletions (25%). Among the base substitutions, transitions (both A· T→ G· C and G· C→ A· T) are strongly favored over transversions (96% versus 4%). Large site-to-site differences are observed among identical base substitutions, presumably reflecting the modulating effects of neighboring bases. The single-base-deletion spectrum is dominated by a large hotspot at a run of adjacent identical base pairs, implying a Streisingerslippage mechanism. The data, when compared to a previously determined wild-type spectrum, also provide information on the specificity of the mismatch repair system.