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Biomedical subjects

F Sherman

Publications and source records attributed to F Sherman.

At least 181 records · Page 10Linked to original sources
PubMed1979

A mutator affecting the region of the iso-1-cytochrome c gene in yeast.

The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity. The simplest hypothesis is that these multisite mutations are deletions, although it has not been excluded that they may involve other types of gross chromosomal aberrations. In contrast, normal strains do not produce such multisite mutations even after mutagenic treatments. The multisite mutations arise at a rate of approximately 10(-5) to 10(-6) per cell per division in DEL1 strains, which is much higher than rates observed for mutation of genes in normal strains. For example, normal strains produce all types of cyc1 mutants at a low rate of approximately 10(-8) to 10(-9). No evidence for multisite mutations was obtained upon analysis of numerous spontaneous ade1, ade2, met2 and met15 mutants isolated in a DEL1 strain. DEL1 appears to be both cis- and trans-dominant. The location of the DEL1 gene and the lack of effect on other genes suggest that the mutator acts only on a region adjacent to itself.

Chromosome Aberrations↗
PubMed1979

Yeast cytochrome c-specific protein-lysine methyltransferase: coordinate regulation with cytochrome c and activities in cyc mutants.

The cytochromes c of fungi and higher plants contain one or two residues of epsilon-N-trimethyllysine, whose biological role is unknown. A cytochrome c-specific S-adenosylmethionine:protein-sysine methyltransferase (methylase) activity was shown to be present in extracts of the bakers' yeast Saccharomyces cerevisiae, and basic kinetic properties of this enzyme are described. The specific activity of the methylase was lower in extracts of cells grown under conditions of catabolite (glucose) repression or anaerobiosis where cytochrome c levels were low, compared with cells grown under derepressed conditions where cytochrome c levels were high. During anaerobic-to-aerobic adaptation, the methylase was induced in parallel with cytochrome c, thus suggesting that the syntheses of cytochrome c and cytochrome c methylase are coordinately regulated. None of the cyc strains surveyed (cyc1, cyc2, cyc3, cyc4, cyc5, and cyc6) had diminished levels of methylase, although some of them were completely or almost completely deficient in cytochrome c.

Cell-Free System↗
PubMed1979

Extrachromosomal psi+ determinant suppresses nonsense mutations in yeast.

The extrachromosomal psi+ determinant in the yeast Saccharomyces cerevisiae enhanced the expression of Mendelian UAA suppressors by 6- to 10-fold. The psi+ determinant by itself is a weak UAA suppressor that caused the production of approximately 1% of the normal level of iso-1-cytochrome c in a strain containing the UAA mutation cycl-72.

Cytochrome c Group↗
PubMed1978

Chromosome mapping of the CYC7 gene determining yeast iso-2-cytochrome c: structural and regulatory regions.

The primary structures of iso-1-cytochrome c and iso-2-cytochrome c in the yeast Saccharomyces cerevisiae are determined by the genes CYC1 and CYC7, respectively. The CYC1 locus was previously shown to be on the right arm of chromosome X, and the CYC7 locus is shown in this investigation to be on the left arm of chromosome V closely linked to the min1 and mak10 markers. The CYC7 locus appears to be composed of a structural region and a regulatory region. Mutations in the structural region can cause a deficiency or alteration of iso-2-cytochrome c, whereas mutations in the regulatory region can cause increases in the amount of iso-2-cytochrome c. Single-site gene conversion, occurring at a relatively high frequency of approximately 4%, caused intragenic recombination of a mutational site in the structural region and a mutational site in the regulatory region, enabling us to suggest the order of the sites in relationship to other markers on the chromosome.

Chromosome Mapping↗
PubMed1978

Deletions of the iso-1-cytochrome c and adjacent genes of yeast: discovery of the OSM1 gene controlling osmotic sensitivity.

Some of the deletions in the yeast Saccharomyces cerevisiae that encompass the CYC1 gene, which determines iso-1-cytochrome c, extend into the OSM1 gene, causing inhibition of growth on hypertonic media, and into the RAD7 gene, causing sensitivity to UV light. Two deletions (cyc1--363 and cyc1--367) encompass only the CYC1 gene, two deletions (cyc1--366 and cyc1--368) encompass the CYC1 and OSM1 genes, three deletions (cyc1--1, cyc1--364 and cyc1--365) encompass the CYC1, OSM1 and RAD7 genes, while none of the deletions extend into the closely linked SUP4 gene.

Cytochrome c Group↗
PubMed1978

A chromosomal translocation causing overproduction of iso-2-cytochrome c in yeast.

The CYC7-1 mutation in the yeast Saccharomyces cerevisiae causes the production of approximately 30 times the normal amount of iso-2-cytochrome c. Genetic analysis established that the CYC7-1 mutation is a reciprocal translocation involving the left arm of chromosome V and the right arm of chromosome XVI. The chromosome V arm was broken adjacent to the gene CYC7, which determines the primary structure of iso-2-cytochrome c, and this fragment containing the CYC7 gene was joined to the segment of chromosome XVI. It appears as though the elevation of iso-2-cytochrome c is caused by an abnormal controlling region adjacent to the structural region of the CYC7 gene.

Cytochrome c Group↗
PubMed1977

Altered absorption spectra of iso-1-cytochromes c from mutants of yeast.

Low temperature (-190 degrees) spectrophotometric recordings were made of mutant strains of the yeast Saccharomyces cerevisiae containing various altered sequences of iso-1-cytochromes c. All mutants with replacements of the tryptophan 64 residue had abnormal Calpha-bands, in which the alpha2-peaks were accentuated to various degrees by being more separated from the major alpha1-peaks and by making up a larger portion of the total Calpha-peak. The altered iso-1-cytochromes c included those having the normal tryptophan 64 replaced by phenylalanine, leucine, tyrosine, cysteine, serine, or glycine as well as those having replacements at position 64 and additional replacements at other sites. Tryptophan 64 in iso-1-cytochrome c, which corresponds to tryptophan 59 in vertebrate cytochromes c, appears to be an important residue for preserving the electronic environment of the heme group. It is uncertain, however, whether altered spectra are due specifically to the abnormal residues at position 64 or due to distorted tertiary structures caused by the replacements.

Amino Acid Sequence↗
PubMed1977

Role of DNA sequences in genetic recombination in the iso-1-cytochrome c gene of yeast. II. Comparison of mutants altered at the same and nearby base pairs.

X-ray-induced mitotic recombination rates and spontaneous meiotic recombination rates have been determined in two-point crosses of various defined cyc1 mutants of the yeast Saccharomyces cerevisiae. All but one of the 17 cyc1 mutants chosen for this study contained either the addition, deletion or substitution of single base-pairs located within a defined segment of the gene that corresponds to the 11 amino acid residues at the amino terminus of iso-1-cytochrome c; approximately half of these mutants had alterations of the AUG initiation codon, some at the same base pair. Up to 66-fold differences in X-ray-induced recombination rates were observed when the same cyc1 mutant was crossed to cyc1 mutants having different alterations in the AUG initiation codon; over a ten-fold difference was observed in series of homologous crosses involving mutants with different changes at the same base-pair. Recombination rates that were associated with specific cyc1 mutants co-segregated with the particular alleles following meiosis, and comparable recombination patterns were also observed for independently isolated, identical mutations. With the mutants used in this study, the frequencies of meiotic recombination did not differ as markedly, suggesting a dissimilar dependence on specific DNA sequences for these two modes of recombination. These disproportionalities of recombination rates suggest that the nature of the mismatched bases influences the recombination process, but not in a way that can be simply interpreted.

Base Sequence↗
PubMed1976

Inhibition of growth by amber suppressors in yeast.

Strains of the yeast Saccharomyces cerevisiae that contain highly efficient amber (UAG) suppressors grow poorly on nutrient medium, while normal or nearly normal growth rates are observed when these strains lose the supressors or when the suppressors are mutated to lower efficiencies. The different growth rates account for the accumulation of mutants with lowered efficiencies in cultures of strains with highly efficient amber suppressors. Genetic analyses indicate that one of the mutations with a lowered efficiency of suppression is caused by an intragenic mutation of the amber supressor. The inhibition of growth caused by excessive suppression is expected to be exacerbated when appropriate suppressors are combined together in haploid cells if two suppressors act with a greater efficiency than a single suppressor. Such retardation of growth is observed with combinations of two UAA (ochre) suppressors (Gilmore 1967) and with combinations of two UAG suppressors when the efficiencies of each of the suppressors are within a critical range. In contrast, combinations of a UAA suppressor and a UAG suppressor do not affect growth rate. Apparently while either excessive UAA or excessive UAG suppression is deleterious to yeast, a moderate level of simultaneous UAA and UAG suppression is not.

Cytochrome c Group↗
PubMed1976

Isolation and characterization of amber suppressors in yeast.

Nonsense suppressors were obtained in a haploid yeast strain containing eight nutritional mutations, that are assumed to be amber or ochre, and the cyc1-179 amber mutation that has a UAG codon corresponding to position 9 in iso-1-cytochrome c. Previous studies established that the biosynthesis and function of iso-1-cytochrome c is compatible with replacements at position 9 of amino acids having widely different structures (Stewart and Sherman 1972). UV-induced revertants, selected on media requiring the reversion of one or two of the amber nutritional markers, were presumed to contain a suppressor if there was the unselected reversion of at least one other marker. The 1088 suppressors that were isolated could be divided into 78 phenotypic classes. Only 43 suppressors of three classes caused the production of more than 50% of the normal amount of iso-1-cytochrome c in the cyc1-179 strain. Genetic analyses indicated that all of these highly efficient amber suppressors are allelic to one or another of the eight suppressors which cause the insertion of tyrosine at ochre (UAA) codons (Gilmore, Stewart and Sherman 1971). Furthermore, only tyrosine has been identified at position 9 in iso-1-cytochrome c in cyc1-179 strains suppressed with these efficient amber suppressors.

Cytochrome c Group↗
PubMed1975

Influence of repair on the specificity of ultraviolet-induced reversion of an ochre alleles of the structural gene for iso-1-cytochrome c.

The specific action of UV on the reversion of the ochre allele cycl-9, in which 21 out of 23 revertants have been shown to arise from A-T-to-G.C transitions at position one in the UAA codon, was found to depend on the function of the RAD6 gene, since cycl-9 reversion occurred by a variety of single-base-pair substitutions in a strain carrying the rad6-1 allele.

Alleles↗