Analysis of mutations induced in the SUP4-o gene of Saccharomyces cerevisiae by cis-diammine dichloroplatinum(II)

Mis, Joseph R.A.; Kunz, Bernard A.

doi:10.1093/carcin/11.4.633

Cited by 27 publications

(15 citation statements)

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“…The present data also show that G:C?T:A transversions occurred in comparable proportions at the 5 0 -and 3 0 -modified guanine of the putative 1,2-d(GpG) adduct (Tables III and IV), in agreement with results of other in vitro studies with eukaryotic cells [de Boer and Glickman, 1989;Mis and Kunz, 1990] and of an in vivo analysis of the mutagenicity of cisplatin in the liver of LacZ plasmidbased transgenic mice [Louro et al, 2002]. In the HPRT gene of cisplatin-treated TK6 cells [Cariello et al, 1992] and in a site-directed mutagenesis assay using codon 13 of the human H-ras gene transiently expressed in a mammalian cell line, the majority of the mutated guanines corresponded to the 3 0 base of the GpG adduct [Pillaire et al, 1994].…”

Section: Mutation Spectrasupporting

confidence: 92%

“…T:A transversions were also the most commonly induced mutations produced by cisplatin d(GpG) adducts in in vitro site-directed mutagenesis studies [Burnouf et al, 1990;Bradley et al, 1993;Yarema et al, 1995]. The prevalence of this mutation is in agreement with results of previous studies carried out in cisplatin-treated bacteria and yeast [Burnouf et al, 1990;Mis and Kunz, 1990;Yarema et al, 1994], and in mammalian cells [Cariello et al, 1992;Pillaire et al, 1994]. However, it disagrees with the results obtained with other bacterial systems.…”

Section: Mutation Spectrasupporting

confidence: 50%

“…The cisplatin mutational spectrum has been described in various prokaryotic and eukaryotic experimental systems, although somewhat inconsistent results have been reported [Brower et al, 1981;Burnouf et al, 1987;de Boer and Glickman, 1989;Mis and Kunz, 1990;Cariello et al, 1992;Pillaire et al, 1994;Louro et al, 2002]. Single base-pair substitutions, especially G:C?T:A and A:T?T:A transversions, are the most common mutations identified in prokaryotes [Brower et al, 1981;Burnouf et al, 1987] and in eukaryotes, in which a small number of single base-pair deletions and insertions were also observed [de Boer and Glickman, 1989;Mis and Kunz, 1990]. In HPRT exon 3 of TK6 lymphoblast cells, the most common mutations were G:C?A:T transitions, followed by G:C?T:A transversions, mainly induced in a run of six guanines [Cariello et al, 1992].…”

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of the mutagenic activity of oxaliplatin and cisplatin in the Hprt gene of CHO cells

Silva

Costa

Dias

et al. 2005

Environ and Mol Mutagen

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Oxaliplatin is a platinum-derived antitumor drug that is active against cisplatin-resistant tumors and has lower overall toxicity than does cisplatin. DNA adduct formation is believed to mediate the cytotoxic activity of both compounds; however, the adducts may also be responsible for mutagenic and secondary tumorigenic activities. In this study, we have compared the mutagenicity of oxaliplatin and cisplatin in the Hprt gene of CHO-K1 cells. Both drugs produced dose-related increases in mutant frequency. For 1-hr treatments, oxaliplatin was less mutagenic than cisplatin at equimolar doses, while similar mutant frequencies were induced at equitoxic doses. Sequencing of mutant Hprt genes indicated that the mutation spectra of both oxaliplatin and cisplatin were significantly different from the spontaneous mutation spectrum (P = 0.014 and P = 0.008, respectively). A significant difference was also observed between the spectra of oxaliplatin- and cisplatin-induced mutations (P = 0.033). Although G:C-->T:A transversion was the most common mutation produced by both compounds, oxaliplatin produced higher frequencies of A:T-->T:A transversion than did cisplatin, most commonly at nucleotide 307, and higher frequencies of small deletions/insertions. Also, cisplatin induced tandem base-pair substitutions, mainly at positions 135/136, and a higher frequency of G:C-->A:T transition than did oxaliplatin. These results provide the first evidence that oxaliplatin is mutagenic and that the profiles of cisplatin- and oxaliplatin-induced mutations display not only similarities but also distinctive features relating to the type and sequence-context preference for mutation. Environ.

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Section: Mutation Spectrasupporting

confidence: 92%

Section: Mutation Spectrasupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of the mutagenic activity of oxaliplatin and cisplatin in the Hprt gene of CHO cells

Silva

Costa

Dias

et al. 2005

Environ and Mol Mutagen

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“…The haploid, repair-proficient yeast strain MKP-op (MATa, canl-100, ade2-1, lys2-1, ura3-52, leu2-3,112, his3-A200, trpl-A901, YCpMP2) (25) and isogenic derivatives deleted either for APNI (apnl-Al:: HIS3) (DRY373-p) (12) (34), transformed into JF1754 by using calcium chloride (25), and isolated from JF1754 by an alkaline extraction procedure (35). SUP4-o alleles were sequenced on double-stranded YCpMP2 molecules (36).…”

Section: Methodsmentioning

confidence: 99%

Specificity of the mutator caused by deletion of the yeast structural gene (APN1) for the major apurinic endonuclease.

Kunz

Henson²,

Roche³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The loss of bases from cellular DNA occurs via both spontaneous and mutagen-induced reactions. The resulting apurinic/apyrimidinic (AP) sites are cytotoxic and mutagenic but are counteracted by repair initiated by AP endonucleases. Previously, in vitro and bacterial transfection studies suggested that AP sites often prompt insertion of dAMP residues during replication, the A-rule. Dissimilar results have been obtained by transfecting DNA into eukaryotic cells. It seemed possible that these differences might be due to idiosyncrasies of transfection or aberrant replication of the transfecting DNA. The observation that AP endonuclease-deficient strains of the yeast Saccharomyces cerevisiae have elevated spontaneous mutation rates allowed us to determine the mutational specificity of endogenously generated AP sites in nuclear DNA. With the yeast SUP4-o gene as a mutational target, we found that a deficiency in the major yeast AP endonuclease, Apnl, provoked mainly single base-pair substitution; the rate of transposon Ty insertion was also enhanced. The rate of transversion to a G-C pair was increased 10-fold in Apnl-deficient yeast, including a 59-fold increase in the rate of AFT -+ CG events. In contrast, the rate of transversion to an AFT pair was increased by only 3-fold. A deficiency in N3-methyladenine glycosylase offset these substitution rate increases, indicating that they are due primarily to AP sites resulting from glycosylase action. Thus, the A-rule does not seem to apply to the mutagenic processing of endogenous abasic sites in S. cereviswae. Other results presented here show that AP endonuclease-deficient Escherichia coi exhibit a mutator phenotype consistent with the A-rule.The loss of DNA bases to form apurinic/apyrimidinic (AP) sites occurs constantly. Such abasic lesions result from the inherent chemical instability of DNA, as well as the incessant assault of endogenous and environmental agents (1). AP sites are formed directly through the slow hydrolysis of the N-glycosyl bonds that anchor bases to DNA, but pyrimidines are lost at a much slower rate than purines (2). Spontaneous and mutagen-induced DNA damages include modified bases that have unstable glycosyl bonds or are substrates for DNA glycosylases, enzymes that remove the damaged bases to generate AP sites (3, 4). AP sites in DNA provide blocks to DNA synthesis and are substrates for mutagenesis in both prokaryotes and eukaryotes (3).The onslaught of AP sites is opposed primarily by the class of repair activities called AP endonucleases (5-8). The predominant forms of these enzymes hydrolyze the phosphodiester bond on the immediate 5' side of an AP site in duplex DNA; the nicked molecule is then further processed by nucleases that remove the dangling 5' AP site, followed by DNA repair synthesis and ligation (4). AP endonucleases and the genes that encode them have been isolated from bacteria, the yeast Saccharomyces cerevisiae, Drosophila melanogaster, and mammalian cells (5-11). In Escherichia coli, exonuclease III and endonuclease...

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“…Supplemented minimal media for growth of yeast strains and selection of SUP4-o mutations were prepared as described previously (44). LA-Ura medium is uracil omission medium but with less adenine (6.65 (36). Bacterial cells were transformed by using calcium chloride (44).…”

mentioning

confidence: 99%

The yeast rad18 mutator specifically increases G.C----T.A transversions without reducing correction of G-A or C-T mismatches to G.C pairs.

1991

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Inactivation of the Saccharomyces cerevisiae RAD18 gene confers a mutator phenotype. To determine the specificity of this effect, a collection of 212 spontaneous SUP4-o mutations arising in a radl8 strain was characterized by DNA sequencing. Comparison of the resulting mutational spectrum with that for an isogenic wild-type (RAD18) strain revealed that the radl8 mutator specifically enhanced the frequency of single base pair substitutions. Further analysis indicated that an increase in the frequency of G.C-*T-A transversions accounted for the elevated SUP4-o mutation frequency. Thus, radl8 is the first eucaryotic mutator found to generate only a particular base pair substitution. The majority of G.C pairs that were not mutated in the radl8 background were at sites where G-C-*T.A events can be detected in SUP4-o, suggesting that DNA sequence context influences the radl8 mutator effect. Transformation of heteroduplex plasmid DNAs into the two strains demonstrated that the radl8 mutator did not reduce the efficiency of correcting G-A or C-T mismatches to G.C pairs or preferentially correct the mismatches to A.T pairs. We propose that the RAD18 gene product might contribute to the fidelity of DNA replication in S. cerevisiae by involvement in a process that serves to limit the formation of G-A and C-T mismatches at template guanine and cytosine sites during DNA synthesis.The RAD18 gene of the yeast Saccharomyces cerevisiae is believed to function in the repair of DNA damage (14). Originally isolated on the basis of increased sensitivity to the lethal effects of UV and X-rays (50), radl8 mutations also sensitize cells to killing by gamma rays (34), the UV mimetic chemical 4-nitroquinoline-1-oxide (46), the folate antagonist trimethoprim (11), the antitumor antibiotic bleomycin (37), and a number of mono-and bifunctional alkylating agents (5,8,30,46). In addition, defects in RAD18 confer a mutator phenotype (48, 61), increase spontaneous, UV-, and gamma ray-induced mitotic recombination (4, 33, 52), enhance the induction of reverse mutation by nitrous acid (46) and decrease UV-, ethylmethanesulfonate-, and 4-nitroquinoline-1-oxide-induced reversion of certain cycl alleles (29,30,46). Furthermore, RAD18 has been found to be semidominant for UV and trimethoprim sensitivity and for enhanced spontaneous and UV-induced mitotic recombination (33), but not for methylmethanesulfonate sensitivity or the mutator phenotype (4, 61).Despite the radiation sensitivity of radl8 strains, they are capable of excising UV-induced pyrimidine dimers and appear to repair gamma ray-induced DNA single-and double-strand breaks (40, 51). However, the efficiency of strand break repair is obscured by a progressive decrease in DNA size during incubation after gamma irradiation (40). There is evidence that a component of postreplication repair in S. cerevisiae requires the RAD18 gene product (9, 47), and it has been suggested that a deficiency in base excision repair subsequent to endonuclease action might account for the cross-sensitivity of radl8...

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Analysis of mutations induced in the SUP4-o gene of Saccharomyces cerevisiae by cis-diammine dichloroplatinum(II)

Cited by 27 publications

References 0 publications

Comparative analysis of the mutagenic activity of oxaliplatin and cisplatin in the Hprt gene of CHO cells

Comparative analysis of the mutagenic activity of oxaliplatin and cisplatin in the Hprt gene of CHO cells

Specificity of the mutator caused by deletion of the yeast structural gene (APN1) for the major apurinic endonuclease.

The yeast rad18 mutator specifically increases G.C----T.A transversions without reducing correction of G-A or C-T mismatches to G.C pairs.

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