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. 1986 Oct;168(1):412–416. doi: 10.1128/jb.168.1.412-416.1986

Analysis of spontaneous base substitutions generated in mismatch-repair-deficient strains of Escherichia coli.

P M Leong, H C Hsia, J H Miller
PMCID: PMC213466  PMID: 3531178

Abstract

We used the lacI system of Escherichia coli to examine the distribution of base substitution mutations occurring spontaneously in different mismatch-repair-deficient strains. The examination of almost 1,200 nonsense mutations generated in strains carrying the mutS, mutH, and mutU alleles confirmed that transitions are highly favored over transversions. The detailed analysis of relative mutation rates at different sites revealed that the pattern of hot spots and cold spots is strikingly similar in each of the three strain backgrounds, strongly supporting the notions that the products of the three genes are part of the same system and that in the absence of any of the components the entire system fails to function. The distribution of mutations occurring in the absence of mismatch repair defined a pronounced topography of the lacI gene. There was no obvious correlation of the hot spots or cold spots with either nearest-neighbor sequences or A X T richness of the immediate surrounding sequence.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer J., Krämmer G., Knippers R. Asymmetric repair of bacteriophage T7 heteroduplex DNA. Mol Gen Genet. 1981;181(4):541–547. doi: 10.1007/BF00428750. [DOI] [PubMed] [Google Scholar]
  2. Benzer S. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE. Proc Natl Acad Sci U S A. 1961 Mar;47(3):403–415. doi: 10.1073/pnas.47.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bourguignon-Van Horen F., Brotcorn A., Caillet-Fauquet P., Diver W. P., Dohet C., Doubleday O. P., Lecomte P., Maenhaut-Michel G., Radman M. Conservation and diversification of genes by mismatch correction and SOS induction. Biochimie. 1982 Aug-Sep;64(8-9):559–564. doi: 10.1016/s0300-9084(82)80087-4. [DOI] [PubMed] [Google Scholar]
  4. Choy H. E., Fowler R. G. The specificity of base-pair substitution induced by the mutL and mutS mutators in E. coli. Mutat Res. 1985 Mar;142(3):93–97. doi: 10.1016/0165-7992(85)90046-6. [DOI] [PubMed] [Google Scholar]
  5. Coulondre C., Miller J. H., Farabaugh P. J., Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. doi: 10.1038/274775a0. [DOI] [PubMed] [Google Scholar]
  6. Coulondre C., Miller J. H. Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues. J Mol Biol. 1977 Dec 15;117(3):525–567. doi: 10.1016/0022-2836(77)90056-0. [DOI] [PubMed] [Google Scholar]
  7. Coulondre C., Miller J. H. Genetic studies of the lac repressor. IV. Mutagenic specificity in the lacI gene of Escherichia coli. J Mol Biol. 1977 Dec 15;117(3):577–606. doi: 10.1016/0022-2836(77)90059-6. [DOI] [PubMed] [Google Scholar]
  8. Cox E. C. Bacterial mutator genes and the control of spontaneous mutation. Annu Rev Genet. 1976;10:135–156. doi: 10.1146/annurev.ge.10.120176.001031. [DOI] [PubMed] [Google Scholar]
  9. Dohet C., Wagner R., Radman M. Repair of defined single base-pair mismatches in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Jan;82(2):503–505. doi: 10.1073/pnas.82.2.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fox M. S. Some features of genetic recombination in procaryotes. Annu Rev Genet. 1978;12:47–68. doi: 10.1146/annurev.ge.12.120178.000403. [DOI] [PubMed] [Google Scholar]
  11. Glickman B. W. Spontaneous mutagenesis in Escherichia coli strains lacking 6-methyladenine residues in their DNA: an altered mutational spectrum in dam- mutants. Mutat Res. 1979 Jul;61(2):153–162. doi: 10.1016/0027-5107(79)90122-2. [DOI] [PubMed] [Google Scholar]
  12. Kramer B., Kramer W., Fritz H. J. Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli. Cell. 1984 Oct;38(3):879–887. doi: 10.1016/0092-8674(84)90283-6. [DOI] [PubMed] [Google Scholar]
  13. Kumura K., Sekiguchi M. Identification of the uvrD gene product of Escherichia coli as DNA helicase II and its induction by DNA-damaging agents. J Biol Chem. 1984 Feb 10;259(3):1560–1565. [PubMed] [Google Scholar]
  14. Lu A. L., Welsh K., Clark S., Su S. S., Modrich P. Repair of DNA base-pair mismatches in extracts of Escherichia coli. Cold Spring Harb Symp Quant Biol. 1984;49:589–596. doi: 10.1101/sqb.1984.049.01.066. [DOI] [PubMed] [Google Scholar]
  15. Lundblad V., Kleckner N. Mismatch repair mutations of Escherichia coli K12 enhance transposon excision. Genetics. 1985 Jan;109(1):3–19. doi: 10.1093/genetics/109.1.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller J. H., Ganem D., Lu P., Schmitz A. Genetic studies of the lac repressor. I. Correlation of mutational sites with specific amino acid residues: construction of a colinear gene-protein map. J Mol Biol. 1977 Jan 15;109(2):275–298. doi: 10.1016/s0022-2836(77)80034-x. [DOI] [PubMed] [Google Scholar]
  17. Miller J. H. Mutational specificity in bacteria. Annu Rev Genet. 1983;17:215–238. doi: 10.1146/annurev.ge.17.120183.001243. [DOI] [PubMed] [Google Scholar]
  18. Nevers P., Spatz H. C. Escherichia coli mutants uvr D and uvr E deficient in gene conversion of lambda-heteroduplexes. Mol Gen Genet. 1975 Aug 27;139(3):233–243. doi: 10.1007/BF00268974. [DOI] [PubMed] [Google Scholar]
  19. Pukkila P. J., Peterson J., Herman G., Modrich P., Meselson M. Effects of high levels of DNA adenine methylation on methyl-directed mismatch repair in Escherichia coli. Genetics. 1983 Aug;104(4):571–582. doi: 10.1093/genetics/104.4.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scheuermann R. H., Echols H. A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7747–7751. doi: 10.1073/pnas.81.24.7747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wagner R., Dohet C., Jones M., Doutriaux M. P., Hutchinson F., Radman M. Involvement of Escherichia coli mismatch repair in DNA replication and recombination. Cold Spring Harb Symp Quant Biol. 1984;49:611–615. doi: 10.1101/sqb.1984.049.01.069. [DOI] [PubMed] [Google Scholar]
  22. Wagner R., Jr, Meselson M. Repair tracts in mismatched DNA heteroduplexes. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4135–4139. doi: 10.1073/pnas.73.11.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]

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