Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli: genetic control and molecular specificity

Pavlov, Youri I.; Суслов, В. В.; Shcherbakova, Polina V.; Kunkel, Thomas A.; Ono, Akira; Matsuda, Akira; Schaaper, Roel M.

doi:10.1016/0027-5107(96)00060-7

Cited by 31 publications

(33 citation statements)

References 48 publications

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“…We observed no prominent induced effects after 24 h. After 48 h of treatment, however, HAP triggered apoptosis became evident. In conformity with the mechanism of mutagenesis via acting as a base analog described in literature (7,9), cell division and therefore DNA replication seemed to be essential for HAP to exert its cytotoxic effects. Nevertheless, the increase of apoptotic cells within control cells without mARC knockdown and cells with mARC1 knockdown was rather modest.…”

Section: Discussionsupporting

confidence: 83%

The Pivotal Role of the Mitochondrial Amidoxime Reducing Component 2 in Protecting Human Cells against Apoptotic Effects of the Base Analog N6-Hydroxylaminopurine

Plitzko

Havemeyer

Kunze

et al. 2015

Journal of Biological Chemistry

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Background:In vitro the mARC-system catalyzes reductions of N-hydroxylated compounds as for instance N-hydroxylated base analogs. Results: mARC2 knockdown increases N 6 -hydroxylaminopurine sensitivity of HeLa cells but N 6 -hydroxyadenosine detoxication is more effectively catalyzed by adenosine deaminase. Conclusion: mARC2 plays a critical role in detoxication of N 6 -hydroxylaminopurine in HeLa cells. Significance: Detoxication of mutagenic N-hydroxylated base analogs may constitute a physiological function of the mARC-system.

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Section: Discussionsupporting

confidence: 83%

The Pivotal Role of the Mitochondrial Amidoxime Reducing Component 2 in Protecting Human Cells against Apoptotic Effects of the Base Analog N6-Hydroxylaminopurine

Plitzko

Havemeyer

Kunze

et al. 2015

Journal of Biological Chemistry

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“…NR11634 is a gal + revertant of NR10234 (galK2), which has been described [21], and was tested for UV sensitivity.…”

Section: Bacterial Strainsmentioning

confidence: 99%

Inhibition of spontaneous mutagenesis by vanillin and cinnamaldehyde in Escherichia coli: Dependence on recombinational repair

Shaughnessy

Schaaper

Umbach

et al. 2006

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that effectively inhibit both induced and spontaneous mutations. We have shown previously that VAN and CIN reduced the spontaneous mutant frequency in Salmonella TA104 (hisG428, rfa, ΔuvrB, pKM101) by approximately 50% and that both compounds significantly reduced mutations at GC sites but not at AT sites. Previous studies have suggested that VAN and CIN may reduce mutations in bacterial model systems by modulating DNA repair pathways, particularly by enhancing recombinational repair. To further explore the basis for inhibition of spontaneous mutation by VAN and CIN, we have determined the effects of these compounds on survival and mutant frequency in five Escherichia coli strains derived from the wild-type strain NR9102 with different DNA repair backgrounds. At nontoxic doses, both VAN and CIN significantly reduced mutant frequency in the wild-type strain NR9102, in the nucleotide excision repair-deficient strain NR11634 (uvrB), and in the recombination-proficient but SOS-deficient strain NR11475 (recA430). In contrast, in the recombination-deficient and SOS-deficient strain NR11317 (recA56), both VAN and CIN not only failed to inhibit the spontaneous mutant frequency but actually increased the mutant frequency. In the mismatch repair-defective strain NR9319 (mutL), only CIN was antimutagenic. Our results show that the antimutagenicity of VAN and CIN against spontaneous mutation required the RecA recombination function but was independent of the SOS and nucleotide excision repair pathways. Thus, we propose the counterintuitive notion that these antimutagens actually produce a type of DNA damage that elicits recombinational repair (but not mismatch, SOS, or nucleotide excision repair), which then repairs not only the damage induced by VAN and CIN but also other DNA damageresulting in an antimutagenic effect on spontaneous mutation.

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“…In E. coli (and Salmonella), hypersensitivity to N-hydroxylated compounds, including hydroxylamine (HA), was found associated with a deletion of the chromosomal uvrB-bio region [13][14][15][16]. Subsequently, it was found that the hypersensitivity of the E. coli Δ(uvrBbio) strains is not due to their uvr excision-repair defect but to their defect in synthesis of the molybdenum cofactor (MoCo) [17].…”

Section: Introductionmentioning

confidence: 99%

Molybdenum cofactor-dependent resistance to N-hydroxylated base analogs in Escherichia coli is independent of MobA function

Kozmin

Schaaper

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Lack of molybdenum cofactor (MoCo) in Escherichia coli and related microorganisms was found to cause hypersensitivity to certain N-hydroxylated base analogs, such as HAP (6-Nhydroxylaminopurine). This observation has lead to a previous proposal that E. coli contains a molybdoenzyme capable of detoxifying such N-hydroxylated analogs. Here, we show that, unexpectedly, deletion of all known or putative molybdoenzymes in E. coli failed to reveal any baseanalog sensitivity, suggesting that a novel type of MoCo-dependent activity is involved. Further, we establish that protection against the analogs does not require the common molybdopterin guaninedinucleotide (MGD) form of the cofactor, but instead the guanosine monophosphate (GMP)-free version of MoCo (MPT) is sufficient.

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Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli: genetic control and molecular specificity

Cited by 31 publications

References 48 publications

The Pivotal Role of the Mitochondrial Amidoxime Reducing Component 2 in Protecting Human Cells against Apoptotic Effects of the Base Analog N6-Hydroxylaminopurine

The Pivotal Role of the Mitochondrial Amidoxime Reducing Component 2 in Protecting Human Cells against Apoptotic Effects of the Base Analog N6-Hydroxylaminopurine

Inhibition of spontaneous mutagenesis by vanillin and cinnamaldehyde in Escherichia coli: Dependence on recombinational repair

Molybdenum cofactor-dependent resistance to N-hydroxylated base analogs in Escherichia coli is independent of MobA function

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