Induction by manganese of mitochondrial antibiotic resistance mutations in yeast

Putrament, Aleksandra; Baranowska, Hanna Maria; Prazmo, Wieslawa

doi:10.1007/bf00269445

Cited by 117 publications

(20 citation statements)

References 39 publications

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“…In this communication, we report the existence of an apurinic endonuclease activity in the inner membrane of yeast mitochondria, which can be extracted from the membrane by high concentrations of detergents. In addition, the study of the properties of the apurinic endonuclease activity has led us to the discovery of a new deoxyribonuclease activity stimulated by manganese, an interesting property, since this divalent cation is highly mutagenic in yeast mitochondria [13]. We show that the apurinic endonuclease activity and the manganese-stimulated deoxyribonuclease are extracted from the mitochondrial membrane with several ot her endonuclease activities, some of which have been reported previously [14.15].…”

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confidence: 62%

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Endonucleases in Yeast Mitochondria

Foury

1982

European Journal of Biochemistry

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An apurinic endonuclease activity has been characterized in yeast mitochondria. It is dependent on Mg2+, stimulated by about 50% in the presence of 50 mM NaCl and inhibited at higher NaCl concentrations. It is located in the inner mitochondrial membrane and requires high concentrations of detergent (1 .5 -3 ' ; / ; ) Triton X-100) to be extracted. The same treatment extracts several other endonuclease activiriey : the two Mg2+-dependent endonuclease activities cleaving double-stranded DNA at pH 7.5 and 5.4 respect ikely, the ethidiumbromide-stimulated endonuclease activity, the endonuclease activity cleaving single-stranded DNA at pH 7.5 [Jacqueniin-Sablon et al.(1 979) Biochrrnistry, 18, 1 I9 -1271, and a manganese-stimulated deoxyribonucleasc activity cleaving double-stranded DNA at pH 7.5 which has been discovered during the present work. Another endonuclease activity cleaving double-stranded DNA at pH 7.5 in the presence of Mg2+, \lightly stimulated by low NaCl concentrations and inhibited by ethidium bromide is extracted from the membrane pellet remaining after the treatment with 1.5% Triton X-100 by a second treatment with 1.5% Triton X-100 plus I M KCI. The presence in the mitochondrial membrane of this apurinic endonuclease activity indicii tc\ that, like nuclear and prokaryotic DNA, yeast mitochondrial DNA is also subject to specialized repair s! \ i k ' i i i s .Cytoplasmic petites (or Q-) which are produced by large deletions of the mitochondrial DNA, accompanied by amplifications of the retained sequences [I] are induced in SaccharotnjmJ.r cerevisiue at very high frequency by a large number of chemical and physical agents [2]. From the genetic and physiological observations that mitochondrial lesions induced by ultraviolet light can be repaired in certain conditions [3,4], although the pyrimidine dimers are not removed by excision repair [5,6], it has been proposed that repair in yeast mitochondria depends mainly on recombination and/or replication of the damaged mitochondrial DNA [S].In order to determine whether specialized repair systems exist in yeast mitochondria, we have choosen to identify an apurinic endonuclease activity, since this type of enzyme has been characterized in a large number of organisms [7-111 and has also been reported in rat liver mitochondria [12]. In this communication, we report the existence of an apurinic endonuclease activity in the inner membrane of yeast mitochondria, which can be extracted from the membrane by high concentrations of detergents. In addition, the study of the properties of the apurinic endonuclease activity has led us to the discovery of a new deoxyribonuclease activity stimulated by manganese, an interesting property, since this divalent cation is highly mutagenic in yeast mitochondria [13]. We show that the apurinic endonuclease activity and the manganese-stimulated deoxyribonuclease are extracted from the mitochondrial membrane with several ot her endonuclease activities, some of which have been reported previously [14.15].Our results lead to the c...

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confidence: 62%

“…(c) Mn2+ induces at high frequency antibiotic-resistant mutations [13] and mit-mutations which are often produced by small deletions [30]. This cation induces also Q- [31].…”

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confidence: 99%

Endonucleases in Yeast Mitochondria

Foury

1982

European Journal of Biochemistry

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“…However, this same metal can have deleterious effects in biological systems. Excessive accumulation of manganese can interfere with calcium metabolism (11) and increase errors during replication of mitochondrial DNA (12,13). In humans manganese is a potent neurotoxin, and industrial uses of manganese have led to cases of "manganism," which is characterized by disturbances in mental processes and symptoms similar to those of Parkinson's disease (14 -16).…”

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confidence: 99%

The Saccharomyces cerevisiae High Affinity Phosphate Transporter Encoded by PHO84 Also Functions in Manganese Homeostasis

Jensen

Ajua-Alemanji

Culotta

2003

Journal of Biological Chemistry

148

132

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In the bakers' yeast Saccharomyces cerevisiae, high affinity manganese uptake and intracellular distribution involve two members of the Nramp family of genes, SMF1 and SMF2. In a search for other genes involved in manganese homeostasis, PHO84 was identified. The PHO84 gene encodes a high affinity inorganic phosphate transporter, and we find that its disruption results in a manganese-resistant phenotype. Resistance to zinc, cobalt, and copper ions was also demonstrated for pho84⌬ yeast. When challenged with high concentrations of metals, pho84⌬ yeast have reduced metal ion accumulation, suggesting that resistance is due to reduced uptake of metal ions. Pho84p accounted for virtually all the manganese accumulated under metal surplus conditions, demonstrating that this transporter is the major source of excess manganese accumulation. The manganese taken in via Pho84p is indeed biologically active and can not only cause toxicity but can also be incorporated into manganese-requiring enzymes. Pho84p is essential for activating manganese enzymes in smf2⌬ mutants that rely on low affinity manganese transport systems. A role for Pho84p in manganese accumulation was also identified in a standard laboratory growth medium when high affinity manganese uptake is active. Under these conditions, cells lacking both Pho84p and the high affinity Smf1p transporter accumulated low levels of manganese, although there was no major effect on activity of manganese-requiring enzymes. We conclude that Pho84p plays a role in manganese homeostasis predominantly under manganese surplus conditions and appears to be functioning as a low affinity metal transporter.

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“…Diverse genetic effects of Mn2+ have been reported. These include the induction of chromosomal gene mutations in prokaryotes (Demerec & Hanson, 1951 ;Orgel & Orgel, 1965) and mitochondria1 mutations in yeast (Putrament et al, 1973(Putrament et al, , 1975. Mn2+ has also been shown to reduce the fidelity of DNA replication in some in vitro systems (Hall & Lehman, 1968; for other references see Loeb et al, 1978 andHibner &Alberts, 1980).…”

Section: Discussionmentioning

confidence: 99%

Modification of Chromosome Instability in Aspergillus nidulans

1982

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2899Strains of Aspergillus nidulans with a chromosome segment in duplicate show instability at mitosis; their colonies produce faster-growing sectors which arise from nuclei with spontaneous deletions in either duplicate segment. In an attempt to probe the deletion process, the effects of mutations causing sensitivity to UV treatment, and those of manganous ions, have been studied in strains carrying either Dp(1,II) or Dp(II1,VIII). For comparison, the effects of Mn2+ on balanced and unbalanced diploids have also been examined. The uvsE allele, which decreases intragenic mitotic crossing over in diploids, increased deletion frequency in strains with either duplication. The uvsB allele, which increases intragenic mitotic crossing over in diploids, increased deletion frequency only in Dp(1,II) strains; in addition, by causing early mitotic crossing over between the homologous segments, it produced some novel deletion products. Mn2+ substantially decreased the deletion frequency in Dp(1,II) strains and decreased mitotic crossing over in diploids; it had no effect on Dp(II1,VIII) strains. The results suggest that in haploid duplication strains there are two classes of spontaneous DNA lesions, recombinogenic and non-recombinogenic, both of which, failing repair, lead to deletion.

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Induction by manganese of mitochondrial antibiotic resistance mutations in yeast

Cited by 117 publications

References 39 publications

Endonucleases in Yeast Mitochondria

Endonucleases in Yeast Mitochondria

The Saccharomyces cerevisiae High Affinity Phosphate Transporter Encoded by PHO84 Also Functions in Manganese Homeostasis

Modification of Chromosome Instability in Aspergillus nidulans

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