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  • 1
    Electronic Resource
    Electronic Resource
    Mutator versus antimutator activity of a T4 DNA polymerase mutant distinguishes two different frameshifting mechanisms (1983)
    Springer
    Molecular genetics and genomics 189 (1983), S. 113-117 
    Details
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Classical “antimutator” DNA polymerases of bacteriophage T4 were examined for their effects upon frameshift mutation rates at a number of positions within rII cistrons. Their antimutagenic activities reduced frameshift frequencies at a number of sites, but at other sites the opposite occurred: the mutant polymerases exhibited clear mutator activities. This dichotomy reveals the operation of two distinct mechanisms of frameshift mutagenesis that are correlated with the DNA sequences at the frameshift sites. Frameshift mutants subject to the antimutator effects of the mutant polymerase lie in A:T-run DNA sequences, where mutations presumably arise by means of the interstrand DNA misalignments postulated by classical theory. The frameshift mutants produced by the mutator activity of these same polymerases lie in quasipalindromic DNA sequences, where mutations are postulated to arise by aberrant metabolism of DNA secondary structures such as hairpins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00326062
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  • 2
    Electronic Resource
    Electronic Resource
    Asymmetric cytosine deamination revealed by spontaneous mutational specificity in an Ung− strain of Escherichia coli (1987)
    Springer
    Molecular genetics and genomics 209 (1987), S. 78-82 
    Details
    ISSN: 1617-4623
    Keywords: Uracil-DNA glycosylase ; Cytosine deamination ; Transcription ; DNA repair ; DNA context
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A collection of 164 spontaneous lacI − mutations were recovered from a uracil-DNA glycosylase deficient (Ung−) strain of Escherichia coli and analyzed by DNA sequencing. As predicted by genetic studies, G:C→A:T transitions predominated among base substitution events. However, DNA sequence analysis indicated that these events did not occur at random. Of the 31 G:C→A:T transitions recovered, 24 involved cytosine residues located in the nontranscribed strand of the gene and 15 of the 31 transitions occurred at cytosines located on the 3′ side of 3 or more A:T base pairs. These differentials likely reflect the more single-stranded character of the non-transcribed strand of the gene and of regions rich in A:T base pairs. In addition, mutation at the frameshift hotspot was altered in the Ung− strain, suggesting a role for DNA repair in the formation of structural intermediates that potentiate these events. Also, the analysis of non-hotspot frameshifts, deletions and duplication showed that many involved local DNA sequence. Specifically, several of the frameshift, deletion and duplication mutations occurred near the sequence 5′-CTGG-3′. Thus, DNA sequence analysis of mutational specificity in an Ung− strain has provided evidence that gene expression, DNA repair and DNA context can all potentially influence the classes and frequencies of spontaneous mutation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00329839
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  • 3
    Electronic Resource
    Electronic Resource
    Mutability of bacteriophage M13 by ultraviolet light: Role of pyrimidine dimers (1982)
    Springer
    Molecular genetics and genomics 185 (1982), S. 404-407 
    Details
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag+ ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334131
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  • 4
    Electronic Resource
    Electronic Resource
    DNA sequence analysis of spontaneous mutation in a PolA1 strain of Escherichia coli indicates sequence-specific effects (1987)
    Springer
    Molecular genetics and genomics 207 (1987), S. 267-272 
    Details
    ISSN: 1617-4623
    Keywords: Mutagenic specificity ; Strand discontinuities ; DNA polymerase I ; DNA replication ; DNA repair
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The sequences of a collection of 261 spontaneous lacI- mutants recovered in a PolA- strain of Escherichia coli have indicated an increase in the frequency of most classes of mutation in this strain. Among base substitutions in lacI, a preference for transversions over transitions was observed. In addition, a single transition in the lac operator was enhanced 8-fold. More significantly, of 18 frameshifts, 12 occurred adjacent to a 5′-GTGG-3′ sequence. Likewise, 15 of 24 deletions and 2 of 10 duplications had 5′-GTGG-3′ sequences at one or both endpoints. We speculate that the prevalence of mutations at these specific sequences reflects the persistence of strand discontinuities that enhance the opportunity for mutagenic mishaps. Further, 5′-GTGG-3′ sequences apparently represent sites where DNA polymerase I is involved in some aspect of DNA metabolism. These results strengthen the view that DNA context contributes an important component to spontaneous mutagenesis and indicate an anti-mutagenic role for DNA polymerase I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00331588
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  • 5
    Electronic Resource
    Electronic Resource
    Specificity of recA441-mediated (tif-1) mutational events (1991)
    Springer
    Molecular genetics and genomics 230 (1991), S. 75-80 
    Details
    ISSN: 1617-4623
    Keywords: recA441 ; SOS-induced transversions ; Frameshift hotspot ; lacI − specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary To investigate the impact of SOS induction on the distribution of spontaneous mutation, 111 recA441-mediated mutations were characterized at the DNA sequence level in the lacI gene of Escherichia coli. A 2.6-fold enhancement in lacI − mutation frequency was observed after induction of the SOS system in the absence of mutagenic treatment, and specific classes of mutational events were induced. G : C → C : G, G : C → T : A and A : T → T : A transversion events were specifically enhanced after SOS induction. A preferential 5′-Y-Purine-3′ neighbouring base specificity for these transversion events is reported here (normalised for mutation of the purine residue). In addition, a preference for transversion events at 5′-C/GTGG-3′ sequences is also observed. Fifty events were recovered at the lacI “frameshift hotspot site” and were equally represented by 4 bp addition and deletion events. This 1:1 ratio deviates significantly from the 4:1 distribution characteristic of spontaneous frameshift mutation in the RecA+ background and is a consequence of the fourfold induction of the (−)4 event. This abberrant distribution was confirmed by oligomeric probing of 474 independent recA441-mediated spontaneous lacI − mutations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00290653
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  • 6
    Electronic Resource
    Electronic Resource
    Spontaneous and 9-aminoacridine-induced frameshift mutagenesis: second-site frameshift mutation within the N-terminal region of thelacI gene ofEscherichia coli (1991)
    Springer
    Molecular genetics and genomics 227 (1991), S. 160-164 
    Details
    ISSN: 1617-4623
    Keywords: Spontaneous frameshifts ; 9-Aminoacridine mutagenesis ; Translation reinitiation ; Negative complementation ; E. coli lacI q-d mutants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A novel forward mutational system, based on the acquisition of an Iq-d dominant phenotype from an initial Iq− recessive state, was used to identify second-site frameshift mutation [±1(±3 n ) events] within the N-terminal region of thelacI gene ofEscherichia coli. The DNA sequences are described of forty-six spontaneous and twenty 9-aminoacridine(9-AA)-induced second site mutations. Although −1 frameshift events dominate both spectra, the nature and site specificity of these events clearly distinguish two mutational distributions. The spontaneous distribution contains two −(A: T) frameshift hotspots; one within a monotonic A5 run (9 occurrences), the other at a 5′-CACAACAAC-3′ sequence (12 occurrences). In contrast 17 of the 20 mutations recovered after 9-AA treatment involve the loss of a G: C pair, 14 of which occur at a single site (5′-CGGGC-3′). The striking specificity of the observed mutational hotspots is of interest since this open genetic target contains similar sequences which were infrequently recovered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00260722
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  • 7
    Electronic Resource
    Electronic Resource
    Mutational specificity and cancer chemoprevention (1996)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 99-107 
    Details
    ISSN: 0730-2312
    Keywords: mutational assays ; mutational spectra ; monitoring mutation in people ; transgenic animals ; lacl ; hprt T-cell clonal assay ; chemoprevention ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Mutational specificity describes the composite of all of the genetic alterations in a collection of mutations arising from a specific treatment. The information includes not only the nature of the genetic change (e.g., a base substitution or a frameshift), but also information about nucleotide position and hence the DNA context. As both the type of DNA damage and its position can be expected to reflect the nature of the chemical and physical mutagen, mutational specificity can be expected to provide insights into mechanisms of mutation. Conversely, mutational spectra should also provide insights into the identity of the mutagen. Indeed, the pioneering work on mutational specificity in Escherichia coli indicates that each physical or chemical treatment produces a unique spectrum of mutations.With the application of biotechnology to the field of genotoxicology, the database of sequenced mutations has become quite substantial. Both in vitro and in vivo data has been obtained following exposure to a variety of agents. In this communication we will critically assess whether the reality of mutational specificity has fulfilled the expectations and to examine what potential remains to be explored, especially in the area of monitoring human populations. The usefulness of both mutational spectra analysis and population monitoring with regards to chemoprevention are discussed. J. Cell. Biochem. 25S:99-107. © 1997 Wiley-Liss, Inc.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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