Disease relevance of HMRA1

• Deletion of this gene resulted in sterility of MATa, but not of MAT alpha cells [1].

High impact information on HMRA1

• MATa preferentially recombines with HML(alpha), located near the left end of chromosome III, but can use HMR(alpha), near the right chromosome end [2].
• MATa donor preference depends on a 700 bp orientation-independent cis-acting recombination enhancer, located 17 kb proximal to HML [2].
• Homothallic switching of the mating-type MATa gene in Saccharomyces cerevisiae results from replacement by gene conversion of MAT-Ya DNA with Y(alpha) sequences copied from one of two unexpressed donors [2].
• Starvation for nitrogen further induced (6- to 8-fold) transcription of IME1, but, as expected, the induction was found only in MATa/MAT alpha or rme1-1/rme1-1 diploids [3].
• RME1 is repressed by a complex of MATa1 and MAT alpha 2 gene products [3].

Biological context of HMRA1

• In Pichia angusta, a homothallic species, we found MATalpha2, MATalpha1, and MATa1 genes adjacent to each other on the same chromosome [4].
• The alpha 2 protein, the product of the MAT alpha 2 cistron, represses various genes specific to the a mating type (alpha 2 repression), and when combined with the MATa1 gene product, it represses MAT alpha 1 and various haploid-specific genes (a1-alpha 2 repression) [5].
• The alpha mating type, but not the slow-growing phenotype, of the aar2 mutant was suppressed by introduction of an intronless MATa1 DNA [6].
• The yeast MATa1 gene contains two introns [7].
• Approximately 30% of the time, an a-like cell could be repaired to a normal MATa genotype if the cell was mated to a RAD52 MAT alpha-inc strain [8].

Anatomical context of HMRA1

• Indirect immunofluorescence revealed that in exponentially growing MATa cells, the majority of Ste6 showed a patchy distribution within the plasma membrane, but a significant fraction was found concentrated in a number of vesicle-like bodies subtending the plasma membrane [9].
• Splicing and spliceosome formation of the yeast MATa1 transcript require a minimum distance from the 5' splice site to the internal branch acceptor site [10].
• Recently, it was reported that simultaneous expression of MATa and MATa genes in haploid cells of Saccharomyces cerevisiae increases microtubule stability [Mol. Gen. Genet. 264 (2000) 300] [11].
• The actin cytoskeleton therefore functions in generation of the bipolar budding pattern and is required specifically for proper selection of bud sites in mother MATa/alpha cells [12].
• We also observed that MATa/alpha actin cytoskeleton mutant daughter cells correctly position their first bud at the distal pole of the cell, but mother cells position their buds randomly [12].

Associations of HMRA1 with chemical compounds

• Transcription of IME1 is induced under starvation for nitrogen and glucose and in the presence of the MATa1 and MATalpha2 gene products [13].
• Heterodimerization of the yeast MATa1 and MAT alpha 2 proteins is mediated by two leucine zipper-like coiled-coil motifs [14].
• In an effort to investigate the source of LOH events, we constructed MATalphacan1Delta::LEU2 and MATa CAN1 haploid yeast strains and examined canavanine-resistance mutations in a MATa CAN1/MATalphacan1Delta::LEU2 heterozygote formed by mating UV-irradiated and nonirradiated haploids [15].
• Triply mutated MATalpha2 protein, alpha2-3A, in which all three major groove-contacting residues are mutated to alanine, is defective in binding DNA alone or in complex with Mcm1 yet binds with MATa1 with near wild-type affinity and specificity [16].
• alpha-factor, one of two peptide hormones responsible for synchronized mating between MATa and MAT alpha-cell types in Saccharomyces cerevisiae, binds to its cell surface receptor and is internalized in a time-, temperature-, and energy-dependent manner (Chvatchko, Y., I. Howald, and H. Riezman. 1986. Cell. 46:355-364) [17].

Physical interactions of HMRA1

• Contacts of the ABF1 protein of Saccharomyces cerevisiae with a DNA binding site at MATa [18].
• Thus, it appears that these mutations interfere with the ability of Ste6p to transport a-factor out of the MATa cell [19].

Enzymatic interactions of HMRA1

• Here we used chromatin immunoprecipitation to monitor the in vivo association of Saccharomyces cerevisiae Rad51p with both the cleaved MATa locus and the HML alpha donor [20].
• In these blocked cells, the HO-cut ends of MATa remained stable for at least 3 h [21].

Regulatory relationships of HMRA1

• It appears that STA1 is a haploid-specific gene that is regulated by MATa1 and a product of the MAT alpha locus and that this regulation occurs at the level of RNA accumulation [22].
• The IME4 transcript was induced in starved MATa/MAT alpha diploids but not in other cell types [23].
• Third, MATa cells expressing a truncated but functional STE2 gene (in which the COOH-terminal 135-hydrophilic residues were deleted) produced a protein detected by cross-linking to 35S-alpha-factor of apparent molecular weight 33,000, close to the size expected for the predicted abbreviated STE2 polypeptide [24].
• Transcription of SME1 was regulated negatively by nitrogen and glucose and positively by MATa/MAT alpha and IME1, another positive regulator gene of meiosis [25].
• The yeast a-factor mating peptide and its transporter Ste6 are normally expressed only in MATa haploid cells [26].

Other interactions of HMRA1

• Although some continuity in the chromosomal location of the MAT locus can be traced throughout hemiascomycete evolution and even to Neurospora, the gene content of the locus has changed with the loss of an HMG domain gene (MATa2) from the MATa idiomorph shortly after HO was recruited [4].
• Although a diploid cell homozygous for the aarl and sir3 mutations and for the MATa, HML alpha, and HMRa alleles showed alpha mating type, it could sporulate and gave rise to asci containing four alpha mating-type spores [5].
• AAR2, a gene for splicing pre-mRNA of the MATa1 cistron in cell type control of Saccharomyces cerevisiae [6].
• The RES1-1 mutation was isolated on the basis of its ability to allow MATa/MAT alpha diploid Saccharomyces cerevisiae cells to express a late sporulation-regulated gene, SPR3, in the presence of excess copies of RME1 [27].
• The MAT alpha and MATa/alpha sfl2 null mutant cells incorporate chitin into the new growth zone in the same way as the alpha-factor-treated MATa cells [28].

Analytical, diagnostic and therapeutic context of HMRA1

• Sequence analysis revealed two ORFs in the MATA locus [29].
• Radiolabeling and immunoprecipitation show that MATa ste6 mutants produce pro-a-factor and mature a-factor intracellularly, but little or no extracellular pheromone [30].
• Using an electrophoretic mobility shift assay, we isolated a chromatographic fraction that contains an activity, named YZbp, which binds to two sequences flanking the recognition sequence at MATalpha and to one sequence overlapping it at MATa [31].
• In tetrad dissection of prototrophic diploids that were obtained by rare mating of hml alpha-1 mutants with a heterothallic strain having the MATa ho HMRa HMLa genotype, many mating-deficient haploid segregants were found, while alpha mating-type segregants were observed in a similar diploid using an hml alpha-2 mutant [32].
• We show that the STE20a gene cosegregates with the MATa mating type in genetic crosses, maps within the mating-type locus on a 1.8-Mb chromosome, and is allelic with the MATalpha locus [33].

References