Reversion of nonsense mutants induced by 4-nitroquinoline-1-oxide in Schizosaccharomyces pombe

Janner, F.; Flury, Fred; Leupold, Urs

doi:10.1016/0027-5107(79)90100-3

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…Therefore 4-NQO mutagenesis can cause all possible single-nucleotide substitutions. In previous 4-NQO mutagenesis studies using tester strains, mutations of adenine were reported as either absent ( Prakash et al 1974 ) or low-frequency events (~7%) and were only significantly different to nonmutagenized control strains in three of six experiments ( Janner et al 1979 ). We found only one occurrence of a deletion and no insertions.…”

Section: Resultsmentioning

confidence: 90%

“…4-NQO was previously reported to induce transitions or transversions of guanine residues and frameshifts in bacteria and yeasts ( Prakash et al 1974 ; Janner et al 1979 ; Rosenkranz and Poirier 1979 ). However, adducts of adenine are also formed and therefore adenine is a possible target ( Galiègue-Zouitina et al 1984 , 1985 ; Bailleul et al 1989 ; Menichini et al 1989 ).…”

Section: Resultsmentioning

confidence: 99%

“…In E. coli and mammalian cells, 4-HAQO adducts are repaired by the nucleotide excision repair pathway ( Ikenaga et al 1975a , b , 1977 ; Ikenaga and Kakunaga 1977 ), and in E. coli the error prone DNA polymerase IV (Pol IV) is the likely cause of sequence changes ( Williams et al 2010 ). Early work to characterize the mutagenic effects of 4-NQO in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe , as well as in the bacteria Salmonella typhimurium and E. coli , relied upon reversion of characterized auxotrophic tester strains, as DNA sequencing technology was not yet readily available ( Prakash et al 1974 ; Janner et al 1979 ; Rosenkranz and Poirier 1979 ). These experiments identified the changes induced by 4-NQO as G:C to A:T transitions, G:C to T:A transversions, and frameshifts ( Prakash et al 1974 ; Janner et al 1979 ; Rosenkranz and Poirier 1979 ).…”

mentioning

confidence: 99%

“…Early work to characterize the mutagenic effects of 4-NQO in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe , as well as in the bacteria Salmonella typhimurium and E. coli , relied upon reversion of characterized auxotrophic tester strains, as DNA sequencing technology was not yet readily available ( Prakash et al 1974 ; Janner et al 1979 ; Rosenkranz and Poirier 1979 ). These experiments identified the changes induced by 4-NQO as G:C to A:T transitions, G:C to T:A transversions, and frameshifts ( Prakash et al 1974 ; Janner et al 1979 ; Rosenkranz and Poirier 1979 ). However, differences in frequency and mutation type varied between species and with 4-NQO concentration ( Rosenkranz and Poirier 1979 ).…”

mentioning

confidence: 99%

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Characterization of the Mutagenic Spectrum of 4-Nitroquinoline 1-Oxide (4-NQO) inAspergillus nidulansby Whole Genome Sequencing

Downes

Chonofsky

Tan

et al. 2014

G3 Genes|Genomes|Genetics

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4-Nitroquinoline 1-oxide (4-NQO) is a highly carcinogenic chemical that induces mutations in bacteria, fungi, and animals through the formation of bulky purine adducts. 4-NQO has been used as a mutagen for genetic screens and in both the study of DNA damage and DNA repair. In the model eukaryote Aspergillus nidulans, 4-NQO−based genetic screens have been used to study diverse processes, including gene regulation, mitosis, metabolism, organelle transport, and septation. Early work during the 1970s using bacterial and yeast mutation tester strains concluded that 4-NQO was a guanine-specific mutagen. However, these strains were limited in their ability to determine full mutagenic potential, as they could not identify mutations at multiple sites, unlinked suppressor mutations, or G:C to C:G transversions. We have now used a whole genome resequencing approach with mutant strains generated from two independent genetic screens to determine the full mutagenic spectrum of 4-NQO in A. nidulans. Analysis of 3994 mutations from 38 mutant strains reveals that 4-NQO induces substitutions in both guanine and adenine residues, although with a 19-fold preference for guanine. We found no association between mutation load and mutagen dose and observed no sequence bias in the residues flanking the mutated purine base. The mutations were distributed randomly throughout most of the genome. Our data provide new evidence that 4-NQO can potentially target all base pairs. Furthermore, we predict that current practices for 4-NQO−induced mutagenesis are sufficient to reach gene saturation for genetic screens with feasible identification of causative mutations via whole genome resequencing.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of the Mutagenic Spectrum of 4-Nitroquinoline 1-Oxide (4-NQO) inAspergillus nidulansby Whole Genome Sequencing

Downes

Chonofsky

Tan

et al. 2014

G3 Genes|Genomes|Genetics

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“…A number of methods have been used to effect DNA damage in yeasts. Double strand breaks can be generated by expression of site-specific endonucleases such as HO [4] , [5] and I-SceI [6] , exposure to chemical agents such as bleomycin-family antibiotics [7] or 4-NQO [8] , or using γ or UV-C irradiation [9] . A wide range of chemical agents can effect nucleotide damage, such as the DNA methylating agent MMS, which generates lesions including N3-methyl adenine that cannot be bypassed by replicative DNA polymerases [10] , potentially leading to fork stalling and collapse.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Imaging of DNA Damage in Yeast Cells Using Ultra-Short Near-Infrared Pulsed Laser Irradiation

et al. 2014

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Analysis of accumulation of repair and checkpoint proteins at repair sites in yeast nuclei has conventionally used chemical agents, ionizing radiation or induction of endonucleases to inflict localized damage. In addition to these methods, similar studies in mammalian cells have used laser irradiation, which has the advantage that damage is inflicted at a specific nuclear region and at a precise time, and this allows accurate kinetic analysis of protein accumulation at DNA damage sites. We show here that it is feasible to use short pulses of near-infrared laser irradiation to inflict DNA damage in subnuclear regions of yeast nuclei by multiphoton absorption. In conjunction with use of fluorescently-tagged proteins, this allows quantitative analysis of protein accumulation at damage sites within seconds of damage induction. PCNA accumulated at damage sites rapidly, such that maximum accumulation was seen approximately 50 s after damage, then levels declined linearly over 200–1000 s after irradiation. RPA accumulated with slower kinetics such that hardly any accumulation was detected within 60 s of irradiation, and levels subsequently increased linearly over the next 900 s, after which levels were approximately constant (up to ca. 2700 s) at the damage site. This approach complements existing methodologies to allow analysis of key damage sensors and chromatin modification changes occurring within seconds of damage inception.

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The genetic fine structure of nonsense suppressors in Schizosaccharomyces pombe

et al. 1979

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Meiotic and mitotic fine-structure maps of two efficient UGA suppressors of Schizosaccharomyces pombe which are known (sup3-e) or inferred (sup9-e) to code for two serine tRNAs carrying the mutant anticodon U*CA (Kohli et al. 1979a, b, Rafalski et al. 1979) are presented. Maps based on spontaneous meiotic, spontaneous mitotic and MMS induced mitotic recombination between the primary site of the anticodon mutation and a number of inactivating second-site mutations are similar. Specific marker effects, which drastically increase the frequency of spontaneous meiotic and mitotic recombination in crosses involving one or the other of four exceptional sites (including the anticodon sites of both sup3-e and sup9-e), disappear when mapping is based on MMS induced mitotic recombination. The meiotic marker effect characterizing the anticodon site of one of the two efficient UGA suppressors (sup3-e) also disappears upon further mutation to an inefficient UAA suppressor allele (sup3-i), as shown by its absence in a fine-structure map based on meiotic recombination between the anticodon mutation of this ochre suppressor allele and a new set of inactivating second-site mutations derived from it.

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Reversion of nonsense mutants induced by 4-nitroquinoline-1-oxide in Schizosaccharomyces pombe

Cited by 6 publications

References 16 publications

Characterization of the Mutagenic Spectrum of 4-Nitroquinoline 1-Oxide (4-NQO) inAspergillus nidulansby Whole Genome Sequencing

Characterization of the Mutagenic Spectrum of 4-Nitroquinoline 1-Oxide (4-NQO) inAspergillus nidulansby Whole Genome Sequencing

Real-Time Imaging of DNA Damage in Yeast Cells Using Ultra-Short Near-Infrared Pulsed Laser Irradiation

The genetic fine structure of nonsense suppressors in Schizosaccharomyces pombe

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