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I Herskowitz

Publications and source records attributed to I Herskowitz.

At least 127 records · Page 7Linked to original sources
PubMed1982

Structure of a yeast pheromone gene (MF alpha): a putative alpha-factor precursor contains four tandem copies of mature alpha-factor.

We have cloned and sequenced a gene (MF alpha) coding for alpha-factor, a tridecapeptide mating factor secreted by yeast alpha cells. A plasmid carrying the MF alpha gene was identified by screening for production of alpha-factor by mat alpha 2 mutants, which fail to secrete alpha-factor because of simultaneous synthesis and degradation of the factor. The cloned segment codes for four mature alpha-factor within a putative precursor of 165 amino acids. The putative precursor begins as a signal sequence for secretion. The next segment, of approximately 60 amino acids, contains three potential glycosylation sites. The carboxy-terminal half of the precursor contains four tandem copies of mature alpha-factor, each preceded by spacer peptides of six or eight amino acids (variations of Lys-Arg-Glu-Ala-Asp-Ala-Glu-Ala), which are hypothesized to contain proteolytic processing signals.

Amino Acid Sequence↗
PubMed1981

Homology and non-homology at the yeast mating type locus.

Four mutations of the alpha mating type locus of Saccharomyces cerevisiae have been analysed to determine their relationship to the a mating type locus. Mat alpha+ recombinations are produced by mat alpha 2-/MAT but not by mat alpha 1-/MATa diploids. MAT alpha and MATa thus contain regions of homology (coding for at least part of MAT alpha 2) and regions of non-homology (coding for at least part of MAT alpha 1)-the genetic determinant for cell type is larger than the non-homologous sequence seen by DNA-DNA heteroduplexes and genetic analysis. The segment transposed in mating type interconversion includes both types of sequence.

Base Sequence↗
PubMed1980

The trans action of HMRa in mating type interconversion.

HML and HMR are the sites of cryptic mating type genes in the yeast Saccharomyces cerevisiae. In the presence of the HO gene, the information from HML or HMR (an a or alpha cassette) is transferred to the mating type locus (MAT). HML, HMR, and MAT are located on chromosome III, yet are widely separated. Similarly, in other yeasts, at least some of the genes involved in mating typing interconversion are linked to the mating type locus. We demonstrate here that a cassette donor (HMR) and the cassette target (MAT) need not be physically linked for successful mating type interconversion. In particular, we show that HMRa on one chromosome can donate an a cassette to the mating type locus on a homologous chromosome III.

Chromosome Mapping↗
PubMed1979

Isolation of a circular derivative of yeast chromosome III: implications for the mechanism of mating type interconversion.

We describe genetic and physical characterization of rearrangements of chromosome III which result in changes of cell type in S. cerevisiae. Two types of rearrangements were obtained as rare events which caused a change at the locus controlling cell type, MAT, associated with a recessive lethal mutation, in one case from MATalpha to MATa-lethal, and in the other case from MATa to MATalpha-lethal. The MATa-lethal mutation is a deletion on the right arm of chromosome III, which we demonstrate extends to (or near) HMalpha. We suggest this deletion removes MATalpha and activates cryptic MATa information stored in HMalpha as proposed in the cassette model of mating type interconversion. The MATalpha-lethal mutation is the result of the formation of a circular chromosome III, which we interpret to remove MATa and activate the cryptic MATalpha information stored at HMa. Strains carrying the MATalpha-lethal chromosome contain a circular chromosome of length 62.6 plus or minus 5.7 mum, which is absent in related strains. This chromosome was confirmed to be chromosome III by hybridization of specific yeast DNA fragments to supercoiled DNA obtained from MATalpha-lethal strains. The isolation of a large circular derivative of chromosome III allows correlation of genetic and physical distance based on large distances-1 centimorgan corresponds to approximately 2700 base pairs.

Chromosome Aberrations↗
PubMed1979

Asymmetry and directionality in production of new cell types during clonal growth: the switching pattern of homothallic yeast.

Homothallic Saccharomyces yeasts efficiently interconvert between two cell types, the mating types a and alpha. These interconversions have been proposed to occur by genetic rearrangement ("cassette" insertion) at the locus controlling cell type (the mating type locus). The pattern of switching from one cell type to the other during growth of a clone of homothallic cells has been followed by direct microscopic observation, and the results have been summarized as "rules" of switching. First, when a cell divides, it produces either two cells with the same mating type as the original cell or two cells that have switched to the other mating type. This observation suggests that the mating type locus is changed early in the cell cycle, in late Gl or during S. Second, the ability to produce cells that have switched mating type is restricted to cells that have previously divided ("experienced cells"). Spores and buds ("inexperienced cells") rarely if ever give rise to cells with changed mating type. A homothallic yeast cell thus exhibits asymmetric segregation of the potential for mating type interconversion--at each cell division, the mother, but not the daughter, is capable of switching cell types in its next division. Homothallic cells also exhibit directionality in switching: experienced cells switch to the opposite cell type in more than 50% of cell divisions. These results show that the process of mating type interconversion is itself controlled during growth of a clone of homothallic cells. By analogy and extension of these results, we propose that multiple cell types can be produced in a specific pattern during development of a higher eucaryote in a model involving sequential cassette insertion.

Animals↗
PubMed1979

Location of the regulatory site for establishment of repression by bacteriophage lambda.

During the lysogenic response to infection by bacteriophage lambda, the phage-specified cII and cIII proteins provide for the coordinate establishment of repression and integration of the viral DNA. One critical regulatory function of cII/cIII is an activation of synthesis of the cI protein, the repressor that maintains lysogeny. The mechanism and site for regulation of the cI gene by cII/cIII have been a subject of controversy. The two principal hypotheses for cII/cIII action are: initiation of new RNA chains in the y region of lambda DNA just to the left of the cII gene; or antitermination of a short leader RNA (4S or oop RNA) initiated to the right of the cII gene. In an effort to distinguish between these hypotheses, we have studied the cII-mediated turn-on of cI protein synthesis in three classes of prophage deletion strains: deletions of the 4S RNA promoter but not the y region, deletions that remove both regions, and deletions that leave both intact. We find that an intact y region is required for normal regulation of the cI gene by cII, but the 4S RNA promoter is not. From experiments with other mutants, we conclude that rightward transcription from the early lytic promoter is also not necessary for positive regulation. Our results suggest that positive regulation by cII/cIII involves initiation of new RNA chains through activation of promoter sites.

Binding Sites↗
PubMed1979

Control of yeast cell types by mobile genes: a test.

The yeast Saccharomyces cerevisiae changes cell types by switching the alleles of the mating type locus (MAT) from a to alpha and vice versa. In the cassette model, these switches, --e.g, from a to alpha--occur when a replica of silent alpha information (an alpha "cassette") replaces the resident a cassette at the mating type locus and is thereby expressed. We have identified a mutation in the locus postulated to be the silent alpha information (HMLalpha) and find that a mutation is introduced into the mating type locus as a result of interconversion: HMLalpha(-) MATalpha cells switch to MATa and then to MATalpha(-). The MATalpha(-) mutation leads to defective mating and behaves like some previously identified MATalpha(-) mutations. These observations satisfy the prediction of the cassette and controlling element models that genetic information is transmitted from HMLalpha to the mating type locus.

Cell Cycle↗
PubMed1979

Healing of mat mutations and control of mating type interconversion by the mating type locus in Saccharomyces cerevisiae.

Homothallic yeasts switch cell types (mating types a and alpha) at high frequency by changing the alleles of the mating type locus, MATa and MATalpha. We have proposed in the cassette model that yeast cells contain silent MATa and MATalpha blocs ("cassettes"), copies of which can be substituted at the mating type locus for the resident information. The existence of silent cassettes was originally proposed to explain efficient switching of a defective MATalpha locus (matalpha) to a functional MATalpha locus. We report here that this "healing" of mat mutations is a general property of the mating type interconversion system and is not specific to the class of matalpha mutations studied earlier: a defective MATa (mata1) switches readily to MATa and various matalpha loci switch readily to MATalpha. These observations satisfy the prediction of the cassette model that all mutations within MATa and MATalpha be healed. These studies also identify MAT functions that control the switching process: the same functions known to promote sporulation and prevent mating in a/alpha cells also inhibit the switching system in a/alpha cells. Finally, we present additional characterization of a natural variant of MATalpha, MATalpha-inc [Takano, I., Kusumi, T. & Oshima, Y. (1973) Mol. Gen. Genet. 126, 19-28] that is insensitive to switching. Our observation that MATalpha-inc acts in cis suggests that it may be altered in a site concerned with excision of MATalpha-inc or its replacement by another cassette.

Journal Article↗