Carcinogen-induced mutation spectrum in wild-type, uvrA and umuC strains of Escherichia coli

Abstract Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

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Sites of preferential induction of cyclobutane pyrimidine dimers in the nontranscribed strand of lacI correspond with sites of UV-induced mutation in Escherichia coli

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)99023-x ◽

1991 ◽

Vol 266 (18) ◽

pp. 11766-11773

Author(s):

D.R. Koehler ◽

S.S. Awadallah ◽

B.W. Glickman

Keyword(s):

Escherichia Coli ◽

Cyclobutane Pyrimidine Dimers ◽

Induced Mutation ◽

Pyrimidine Dimers

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Escherichia coli MutM Suppresses Illegitimate Recombination Induced by Oxidative Stress

Genetics ◽

10.1093/genetics/151.2.439 ◽

1999 ◽

Vol 151 (2) ◽

pp. 439-446 ◽

Cited By ~ 2

Author(s):

Masaaki Onda ◽

Katsuhiro Hanada ◽

Hirokazu Kawachi ◽

Hideo Ikeda

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Hydrogen Peroxide ◽

Dna Damage ◽

Double Strand Breaks ◽

Illegitimate Recombination ◽

Recombination Analysis ◽

Wild Type ◽

Strand Breaks ◽

In The Wild

Abstract DNA damage by oxidative stress is one of the causes of mutagenesis. However, whether or not DNA damage induces illegitimate recombination has not been determined. To study the effect of oxidative stress on illegitimate recombination, we examined the frequency of λbio transducing phage in the presence of hydrogen peroxide and found that this reagent enhances illegitimate recombination. To clarify the types of illegitimate recombination, we examined the effect of mutations in mutM and related genes on the process. The frequency of λbio transducing phage was 5- to 12-fold higher in the mutM mutant than in the wild type, while the frequency in the mutY and mutT mutants was comparable to that of the wild type. Because 7,8-dihydro-8-oxoguanine (8-oxoG) and formamido pyrimidine (Fapy) lesions can be removed from DNA by MutM protein, these lesions are thought to induce illegitimate recombination. Analysis of recombination junctions showed that the recombination at Hotspot I accounts for 22 or 4% of total λbio transducing phages in the wild type or in the mutM mutant, respectively. The preferential increase of recombination at nonhotspot sites with hydrogen peroxide in the mutM mutant was discussed on the basis of a new model, in which 8-oxoG and/or Fapy residues may introduce double-strand breaks into DNA.

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Ribonucleoside and deoxyribonucleoside triphosphate pools during 2-aminopurine mutagenesis in T4 mutator-, wild type-, and antimutator-infected Escherichia coli.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)88826-3 ◽

1985 ◽

Vol 260 (11) ◽

pp. 6618-6622

Author(s):

R L Hopkins ◽

M F Goodman

Keyword(s):

Escherichia Coli ◽

Wild Type ◽

Deoxyribonucleoside Triphosphate

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Phage genetic sites involved in lambda growth inhibition by the Escherichia coli rap mutant.

Genetics ◽

10.1093/genetics/121.3.401 ◽

1989 ◽

Vol 121 (3) ◽

pp. 401-409

Author(s):

P Guzmán ◽

G Guarneros

Keyword(s):

Escherichia Coli ◽

Growth Inhibition ◽

Phage Genome ◽

Bacteriophage Lambda ◽

Phage Lambda ◽

Wild Type ◽

Attp Site

Abstract The rap mutation of Escherichia coli prevents the growth of bacteriophage lambda. We have isolated phage mutants that compensate for the host deficiency. The mutations, named bar, were genetically located to three different loci of the lambda genome: barI in the attP site, barII in the cIII ea10 region, and barIII within or very near the imm434 region. The level of lambda leftward transcription correlates with rap exclusion. Phage lambda mutants partially defective in the pL promoter or in pL-transcript antitermination showed a Bar- phenotype. Conversely, mutants constitutive for transcription from the pI or pL promoters were excluded more stringently by rap bacteria. We conclude that rap exclusion depends on the magnitude of transcription through the wild type bar loci in the phage genome.

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