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  • 1
    ISSN: 1432-0983
    Keywords: S. cerevisiae ; Mating type switching ; Fluctuation assay ; Na-butyrate ; Intrachromosomal gene conversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fluctuation assay of Luria and Delbrück was adapted for the exact determination of mating-type interconversion rates of semi-sterile heterothallic strains of Saccharomyces cereviae. These rates varied between 10−7 and 10−6, depending on the individual strain, and were enhanced in a dose-dependent manner for cells growing in the presence of increasing concentrations of sodium butyrate. Under our experimental conditions, the distribution of alpha cells over populations of a(ste2) cells corresponded to a Poissonian distribution (within sample errors); that over populations of a(ste14)-cells did not differ significantly from the distribution calculated by Lea and Coulsen.
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  • 2
    ISSN: 1432-0983
    Keywords: Key words Starvation  ;  Petite  ;  Adaptive mutation  ;  Respiratory deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Auxotrophic yeast cells were starved on solid media for their respective essential amino acid in the course of “adaptive mutation” experiments. Thereby, high proportions of mitochondrially respiratory deficient (rho−) mutants accumulated among the cells stressed on selective plates. Using a strain with a plus-four frameshift mutation in a chromosomal gene involved in lysine biosynthesis, we observed that many of the revertant colonies which arose late under the selective pressure were composed of mixtures of rho+ and rho− cells, indicating that they originated from founder cells containing intact as well as defective mitochondrial genomes. We show that in spite of the slower growth of rho− cells the late-appearing colonies cannot be interpreted as descending from rho− revertants present before selective plating.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 69 (1982), S. 107-113 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Notes: Abstract This essay examines the possibility of merging the mutation theory of cancer with the hypothesis that cancer is a change in the state of the differentiation of cells. It is suggested that during normal development DNA rearrangements occur, concerning genes which code for differentiation specific cell communication proteins. These proteins are responsible for the proper functioning of growth control in a multicellular organism. DNA-damaging agents — mutagens — induce DNA repair enzymes, some of which may catalyse illegitimate genome rearrangements, thus leading to a change of the balance between growth and differentiation. A cell with a selective advantage may arise and become the origin of a tumor.
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  • 4
    ISSN: 1617-4623
    Keywords: Key words Replication-independent mutation ; Petite ; Starvation-associated mutation ; Hypermutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Adaptive or selection-induced mutations are defined as mutations that occur in non-dividing cells as a response to prolonged non-lethal selective pressure such as starvation for an essential amino acid. In the absence of DNA replication, the processing of endogenous DNA lesions by repair enzymes probably acts as a source of mutations. We are studying selection-induced reversions of frameshift alleles in the eukaryote Saccharomyces cerevisiae. Here we show that respiration-deficient strains, totally devoid of mitochondrial DNA, yield selection-induced mutants at slightly elevated frequencies compared to isonucleic respiration-competent strains. Therefore factors of mitochondrial origin such as reactive oxygen species or hypothetical recombinogenic DNA fragments are unlikely to be mediators of selection-induced nuclear frameshift mutation in yeast. Furthermore we compared sequence spectra of reversions of the +1 hom3-10 frameshift allele and found a strong preference for −1 deletions in mononucleotide repeats in selection-induced and replication-dependent revertants, indicating slippage errors during DNA repair synthesis as well as during DNA replication. Remarkably, a higher degree of variation in the site of the reverting frameshift and accompanying base substitutions was found among selection-induced revertants.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 126 (1973), S. 71-74 
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The respiratory deficient mutants induced by methotrexate are shown by genetic analysis to be cytoplasmic petites of both neutral and suppressive types. Mitochondrial DNA is shown to be present in the suppressive mutants tested while in the neutral petites, DNA was only detected in one case.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 186 (1982), S. 512-517 
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A procedure for the determination of the frequency of mating type switching in heterothallic strains of Saccharomyces cerevisiae was worked out. In cell populations irradiated with X-rays the frequencies of switching were enhanced in a dose-dependent manner. The possible implication of this finding for understanding the mechanism of carcinogenesis is discussed.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 207 (1987), S. 320-327 
    ISSN: 1617-4623
    Keywords: Cell cycle ; DNA damage ; Carcinogenesis ; Yeast ; cdc2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Pedigree analyses of individual yeast cells recovering from DNA damage were performed and time intervals between morphological landmark events during the cell cycle (bud emergence and cell separation), were recorded for three generations. The associated nuclear behavior was monitored with the aid of DAPI staining. The following observations were made: (1) All agents tested (X-rays, MMS, EMS, MNNG, nitrous acid) delayed the first bud emergence after treatment, which indicates inhibition of the initiation of DNA replication. (2) Cells that survived X-irradiation progressed further through the cell cycle in a similar way to control cells. (3) Progress of chemically treated cells became extremely asynchronous because surviving cells stayed undivided for periods of varying length. (4) Prolongation of the time between bud emergence and cell separation was most pronounced for cells treated with the alkylating agents MMS and EMS. This is interpreted as retardation of ongoing DNA synthesis by persisting DNA adducts. (5) Cell cycle prolongation in the second and third generation after treatment was observed only with MMS treated cells. (6) In all experiments, individual cells of uniformly treated populations exhibited highly variable responses.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 126 (1973), S. 61-70 
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The folic acid analogue, methotrexate, was found to be an effective inducer of the cytoplasmic petite mutation in different strains of S. carlsbergensis and S. cerevisiae. The induction varies considerably from strain to strain and also with growth conditions under which the experiments are carried out. Determination of mitochondrial protein synthesis in the presence of methotrexate shows a considerable decrease in incorporation of radioactive leucine before any significant induction of petites has taken place. These results and a comparison with results from other laboratories obtained with different drugs provide the basis for a proposed mechanism of petite induction by methotrexate.
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  • 9
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In a yeast mutant (198 D1) exhibiting temperature sensitive DNA replication, incubation at the restrictive temperature influences both nuclear and mitochondrial DNA synthesis but to different degrees, the mitochondrial DNA being less affected. DNA polymerase activities measurable in mitochondria free cell extracts as well as in the extract from isolated mitochondria are found to be unaffected at the restrictive temperature. The level of DNA polymerase in the cell extract is elevated in comparison to the wild type strain. Furthermore, the tight coupling of DNA replication to protein synthesis usually observed in yeast is partly lost in the mutant.
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  • 10
    ISSN: 1617-4623
    Keywords: Intrachromosomal and interchromosomal recombination ; Saccharomyces cerevisiae ; RAD18
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The frequency of intra- and interchromosomal recombination was determined in RAD18 and rad18 deletion and rad18-3 mutant strains. It was found that spontaneous interchromosomal recombination at trp5, his1, ade2, and MAT was elevated 10- to 70-fold in the rad18-3 and rad18Δ mutants as compared to the RAD + strains. On the other hand the frequencies of spontaneous intrachromosomal recombination for the his3Δ3′, his3Δ5′ and the his4C −, his4A − duplications and for heterothallic mating type switching were only marginally elevated in the rad18 deletion mutant, and recombination between ribosomal DNA repeats was only 2-fold elevated in the rad18-3 mutant. These differences may be due to a haploid versus diploid specific difference. However interchromosomal recombination was elevated 40-fold and intrachromosomal recombination was only marginally (1.5-fold) elevated in a diploid homozygous for rad18Δ, arguing against a haploid versus diploid specific difference. Possible explanations for the difference in the elevated levels of intra- versus interchromosomal spontaneous recombination are discussed.
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