The isolation and genetic characterization of extrachromosomal chloramphenicol and oligomycin-resistant mutants from the petite-negative yeast Kluyveromyces lactis

Brunner, Aurora; Cobos, Alba Tuena de; Griffiths, David E.

doi:10.1007/bf00268816

Cited by 21 publications

(5 citation statements)

References 23 publications

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“…Some nuclear mutations have also been described in an early report (23). Such stable mutations seem to exist also in K.lactis which are of either cytoplasmic or nuclear origin (4).…”

Section: Discussionmentioning

confidence: 81%

Genetic Instability of an oligomycin resistanee mutation in yeast is associated with an amplification of a mitochondrial DNA segment

Ragnini-Wilson

Fukuhara

1989

Nucl Acids Res

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In the yeast Kluyveromyces lactis, mutations affecting mitochondrial functions are often highly unstable. In order to understand the basis of this genetic instability, we examined the case of an oligomycin resistant mutant. When the mutant was grown in the absence of the drug, the resistance was rapidly lost. This character showed a typical cytoplasmic inheritance. The unstable resistance was found to be associated with the presence of a repetitive DNA in which the repeating unit was a specific segment of the mitochondrial DNA. The amplified molecules were co-replicating with the wild type genome in the mutant cells. The spontaneous loss of the drug resistance was accompanied by the disappearance of the amplified DNA. The repetitive sequence came from a 405 base-pair segment immediately downstream of a cluster of two transfer RNA genes (threonyl 2 and glutamyl). Modified processing of these tRNAs was detected in the mutant. A possible mechanism by which these events could lead to drug resistance is discussed.

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“…Some nuclear mutations have also been described in an early report (23). Such stable mutations seem to exist also in K.lactis which are of either cytoplasmic or nuclear origin (4).…”

Section: Discussionmentioning

confidence: 81%

Genetic Instability of an oligomycin resistanee mutation in yeast is associated with an amplification of a mitochondrial DNA segment

Ragnini-Wilson

Fukuhara

1989

Nucl Acids Res

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“…Within species, most of the variation in fungal mitochondrial genomes has been attributed to the presence or absence of insertional elements (Taylor 1986;Hudspeth 1992), some of which may facilitate mtDNA recombination (Schmidt et al 1994). In contrast to the limited investigations of mtDNA mutation rates in fungi, there is ample evidence from laboratory experiments that heteroplasmy is accompanied by recombination in the mtDNA of several ascomycetes (Dujon et al 1974;Rowlands & Turner 1975;Belcour & Begel 1977;Brunner et al 1977;Mannella & Lambowitz 1978;Seitz-Mayr et al 1978) and one basidiomycete (Baptista-Ferreira et al 1983). An argument for low mutation rate in mtDNA of A. gallica can be made as follows.…”

Section: Discussionmentioning

confidence: 99%

“…Although recombination of fungal mtDNA has long been known to occur with the formation of heteroplasmons in laboratory experiments (Dujon et al 1974;Rowlands & Turner 1975;Belcour & Begel 1977;Brunner et al 1977;Mannella & Lambowitz 1978;Seitz-Mayr et al 1978;Baptista-Ferreira et al 1983;Collins & Saville 1990;Fukuda et al 1995;Chung et al 1996), no studies, to our knowledge, have asked whether or not recombination of mtDNAs actually occurs in nature. In animals, the prevailing view has been that mtDNAs are maternally inherited and evolve clonally.…”

Section: Introductionmentioning

confidence: 97%

Genetic exchange and recombination in populations of the root‐infecting fungus Armillaria gallica

1996

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Genetic individuals, or genets, of Armillaria and other root-infecting basidiomycetes are usually found in discrete patches that often include the root systems of several adjacent trees. Each diploid individual is thought to arise in an unique mating event and then grow vegetatively in an expanding territory over a long period of time. Our objective in this study was to describe the population from which such genetic individuals are drawn. In a sample including 274 collections representing 121 genetic individuals of A. gallica (synonym A. bulbosa) from two sites in each of four regions of eastern North America, genotype frequencies at seven nuclear loci were not significantly different from Hardy-Weinberg expectations. Furthermore, allele frequencies at the seven loci were not significantly different between regions. Additional allelic data from four non-contiguous regions of mitochondrial DNA showed little or no population subdivision over the four regions. Analysis of the distribution of multilocus mtDNA haplotypes revealed some clonal transmission of mtDNAs between genets and nonrandom mating within sites. Despite the sharing of mtDNA types by some individuals, the overall sample contained a high level of genotypic diversity. The apparent linkage equilibrium between some pairs of loci and the high level of phylogenetic inconsistency among all four loci suggest the occurrence heteroplasmy and recombination among mtDNAs of A. gallica in nature. In laboratory matings of two haploid strains with different mtDNA types, a low frequency of recombination in mtDNA was detected.

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“…This screening procedure was based on observations that the majority of oligomycin-resistant mutants in S. cerevisiae and K. lactis occur in the mitochondrial DNA-encoded subunits 6 and 9 of the ATP synthase F 0 complex (62)(63)(64)(65). By this means we hoped to examine whether any structural and functional alterations in the F 0 subunits would affect the integrity of the mitochondrial genome.…”

Section: Identification Of K Lactis Nuclear Mutations Conferring Olimentioning

confidence: 99%

Positive and Negative Control of Multidrug Resistance by the Sit4 Protein Phosphatase in Kluyveromyces lactis

Chen¹,

Bauer²,

Kuchler³

et al. 2000

Journal of Biological Chemistry

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The nuclear gene encoding the Sit4 protein phosphatase was identified in the budding yeast Kluyveromyces lactis. K. lactis cells carrying a disrupted sit4 allele are resistant to oligomycin, antimycin, ketoconazole, and econazole but hypersensitive to paromomycin, sorbic acid, and 4-nitroquinoline-N-oxide (4-NQO). Overexpression of SIT4 leads to an elevation in resistance to paromomycin and to lesser extent tolerance to sorbic acid, but it has no detectable effect on resistance to 4-NQO. These observations suggest that the Sit4 protein phosphatase has a broad role in modulating multidrug resistance in K. lactis. Expression or activity of a membrane transporter specific for paromomycin and the ABC pumps responsible for 4-NQO and sorbic acid would be positively regulated by Sit4p. In contrast, the function of a Pdr5-type transporter responsible for ketoconazole and econazole extrusion, and probably also for efflux of oligomycin and antimycin, is likely to be negatively regulated by the phosphatase. Drug resistance of sit4 mutants was shown to be mediated by ABC transporters as efflux of the anionic fluorescent dye rhodamine 6G, a substrate for the Pdr5-type pump, is markedly increased in sit4 mutants in an energy-dependent and FK506-sensitive manner.The occurrence of multidrug resistance (MDR) 1 is one of the main obstacles to the successful treatment of cancer. When treated with chemotherapeutic drugs, many cancer cells develop resistance to a variety of structurally and functionally unrelated compounds (for review, see Ref. 1). In most cases, MDR is mediated by an increased expression of the integral membrane multidrug transporters (reviewed in Refs. 2-4). These membrane proteins, known as ATP-binding cassette (ABC) transporters, function in an ATP-dependent way probably by increasing drug efflux and consequently lowering their intracellular accumulation. In a similar manner, many pathogenic microorganisms such as Candida albicans and Plasmodium falciparum can use the ABC transporter-mediated drug efflux mechanism to evade chemotherapy (5-8). However, despite the rapidly growing number of ABC transporters identified in various organisms, little is known about how activities of the drug transporters are modulated and how aberrant regulation of the expression of ABC transporter genes contributes to the acquisition of MDR in vivo.The ABC transporter-mediated drug efflux mechanism is evolutionarily conserved and occurs in a variety of living organisms ranging from bacteria to humans. An example is a recent work demonstrating that the Lactococcus lactis ABC transporter LmrA is able to confer MDR in human cells (9). The recently completed genome sequencing project of Saccharomyces cerevisiae has revealed the presence of as many as 29 proteins belonging to the ubiquitous ABC superfamily (10) that transport a wide range of chemical compounds (11,12). The yeast ABC proteins so far characterized, such as Pdr5, Snq2, Ycf1 and Yor1, confer MDR with physiological and biochemical properties very similar to the human MDR1-en...

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The isolation and genetic characterization of extrachromosomal chloramphenicol and oligomycin-resistant mutants from the petite-negative yeast Kluyveromyces lactis

Cited by 21 publications

References 23 publications

Genetic Instability of an oligomycin resistanee mutation in yeast is associated with an amplification of a mitochondrial DNA segment

Genetic Instability of an oligomycin resistanee mutation in yeast is associated with an amplification of a mitochondrial DNA segment

Genetic exchange and recombination in populations of the root‐infecting fungus Armillaria gallica

Positive and Negative Control of Multidrug Resistance by the Sit4 Protein Phosphatase in Kluyveromyces lactis

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