New cell cycle-regulated genes in the yeast Saccharomyces cerevisiae.
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Amino Acid Sequence↗
Biomedical subjects
T Schuster
Publications and source records attributed to T Schuster.
The mouse poly(C)-binding protein exists in multiple isoforms and interacts with several RNA-binding proteins.
The murine poly(C)-binding protein (mCBP) was previously shown to belong to the group of K-homology (KH) proteins by virtue of its homology to hnRNP-K. We have isolated cDNA-splice variants of mCBP which differ by two variable regions of 93 bp and/or 39 +/- 3 bp respectively. Both variable regions are located between the second and third KH-domain of mCBP. The characterization of a partial genomic clone enabled us to propose a model for the generation of the second variable region by the use of a putative alternative splice signal. The mCBP mRNA is expressed ubiquitously and the protein is found predominantly in the nucleus with the exception of the nucleoli. We have identified five proteins which interact with mCBP in the yeast two hybrid system: mouse y-box protein 1 (msy-1), y-box-binding protein, hnRNP-L, filamin and splicing factor 9G8. The interaction between mCBP and splicing factor 9G8 was confirmed in vivo. These results suggest a function of mCBP in RNA metabolism.
Animals↗
Testicular germ cell tumors in patients with human immunodeficiency virus infection.
BACKGROUND: There has been evidence of a higher incidence of testicular germ cell tumors (GCT) in human immunodeficiency virus (HIV)-seropositive men than in the non HIV-infected male population. Most authors recommend standard therapy for HIV-positive patients with GCT but the immumosuppressive effects of chemotherapy and/or radiotherapy must be considered. METHODS: The records of all patients in whom testicular cancer was diagnosed and/or treated at a single institution between January 1986 and July 1995 were reviewed with regard to HIV seropositivity. Tumor histology, initial staging, treatment, and the patients' outcomes were analyzed in connection with a review of the literature. RESULTS: Six patients with GCT and documented HIV seropositivity at the time of tumor diagnosis (four homosexuals, one bisexual, and one heterosexual former intravenous drug abuser) of 192 documented cases of testicular cancer are reported. In addition, 1 patient proved to be HIV seropositive 34 months after completing chemotherapy (vinblastine, ifosfamide, and cisplatin) for Stage IIB (minimal disease) seminoma. Intensified platinum-based chemotherapy was administered to two patients with clinical Stage IIIC (advanced disease) nonseminomatous germ cell tumors (NSGCT). Both patients achieved a transient partial response but suffered from progressive HIV disease and died 24 and 7 months, respectively, after orchiectomy. One patient with Stage IIIA (moderate disease) seminoma received four courses of chemotherapy (etoposide, ifosfamide, and cisplatin) and has remained in complete remission for 40 months. One patient with bilateral Stage I seminoma underwent adjuvant radiotherapy but was lost to follow-up. One patient with clinical Stage IIA (minimal disease) NSGCT refused any further treatment after hemiorchiectomy, but four courses of chemotherapy (cisplatin, etoposide and bleomycin) had to be given 32 months later because of symptomatic abdominal disease. A partial remission was obtained and there was no evidence of active tumor 16 months after the completion of chemotherapy. A retroperitoneal lymph node dissection was performed in 1 patient with Stage I NSGCT who was free of disease 111 months after diagnosis. The Centers for Disease Control classification for HIV infection and acquired immune deficiency syndrome (AIDS) did not change after therapy in two patients, whereas three patients suffered from progressive HIV disease. CONCLUSIONS: HIV infection should be considered in patients with testicular cancer who belong to an urban population. Oncologic therapy based on a patient's individual situation is recommended.
Adult↗
Chronic recurrent multifocal osteomyelitis (CRMO).
Pathogenesis of CRMO still remains unknown. Characteristic, but not pathognomonic for this syndrome are clinical course (age, sex, chronic recurrent, intermittent course), radiological findings (metaphyseal lesions), histology (chronic osteomyelitis without colliquation) and microbiological results (lack of pathogen, infectious agents). Favorable, self-limited long-term prognosis of CRMO has been assumed. Antibiotics provide no improvement. Course, severity and recurrency can be influenced positively by antiphlogistic substances, although this has not yet been proved. Whether surgical intervention beyond biopsies might cause improvement on the follow-up is unknown. Our experience (4 cases), and the literature demonstrate great clinical importance that unusual types of osteomyelitis (OM) can be within the differential diagnosis of multifocal osteolytic changes.
Adolescent↗
EGT2 gene transcription is induced predominantly by Swi5 in early G1.
In a screen for cell cycle-regulated genes in the yeast Saccharomyces cerevisiae, we have identified a gene, EGT2, which is involved in cell separation in the G1 stage of the cell cycle. Transcription of EGT2 is tightly regulated in a cell cycle-dependent manner. Transcriptional levels peak at the boundary of mitosis and early G1 The transcription factors responsible for EGT2 expression in early G1 are Swi5 and, to a lesser extent, Ace2. Swi5 is involved in the transcriptional activation of the HO gene during late G1 and early S phase, and Ace2 induces CTS1 transcription during early and late G1 We show that Swi5 activates EGT2 transcription as soon as it enters the nucleus at the end of mitosis in a concentration-dependent manner. Since Swi5 is unstable in the nucleus, its level drops rapidly, causing termination of EGT2 transcription before cells are committed to the next cell cycle. However, Swi5 is still able to activate transcription of HO in late G1 in conjunction with additional activators such as Swi4 and Swi6.
Amino Acid Sequence↗
Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.
Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (< 20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with medJ/+mice. The new allele is designated medTgNA4Bs (medtg). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells.
Animals↗
The tetratricopeptide repeat-domain of the PAS10 protein of Saccharomyces cerevisiae is essential for binding the peroxisomal targeting signal-SKL.
The PAS10 gene was found in a two-hybrid screen for the isolation of genes encoding proteins which interact with the C-terminal peroxisomal targeting signal -SKL. The PAS10 protein is known to be involved in import of proteins into peroxisomes and to contain a tetratricopeptide repeat (TPR) domain. All TPR-containing proteins involved in diverse processes like mitosis or RNA-synthesis share the ability to interact with other proteins. Here we show that the PAS10 protein interacts in vivo with the C-terminal peroxisomal targeting signal. The part essential for this interaction contains the complete tetratricopeptide repeat domain.
Amino Acid Sequence↗
Differential expression of synaptophysin and synaptoporin during pre- and postnatal development of the rat hippocampal network.
The closely related synaptic vesicle membrane proteins synaptophysin and synaptoporin are abundant in the hippocampal formation of the adult rat. But the prenatal hippocampal formation contains only synaptophysin, which is first detected at embryonic day 17 (E17) in perikarya and axons of the pyramidal neurons. At E21 synaptophysin immunoreactivity extends into the apical dendrites of these cells and in newly formed terminals contacting these dendrites. The transient presence of synaptophysin in axons and dendrites suggests a functional involvement of synaptophysin in fibre outgrowth of developing pyramidal neurons. Synaptoporin expression parallels the formation of dentate granule cell synaptic contacts with pyramidal neurons: the amount of hippocampal synaptoporin, determined in immunoblots and by synaptoporin immunostaining of developing mossy fibre terminals; increases during the first postnatal week. Moreover, in the adult, synaptoporin is found exclusively in the mossy fibre terminals present in the hilar region of the dentate gyrus and the regio inferior of the cornu ammonis. In contrast, synaptophysin is present in all synaptic fields of the hippocampal formation, including the mossy fibre terminals, where it colocalizes with synaptoporin in the same boutons. Our data indicate that granule neuron terminals differ from all other terminals of the hippocampal formation by the presence of both synaptoporin and synaptophysin. This difference, observed in the earliest synaptic contacts in the postnatal hippocampus and persisting into adult life, suggests distinct functions of synaptoporin in these nerve terminals.
Animals↗
Decrease of gap junction number in the rat neural tube between ED 11 and ED 15.
The apical regions of neuroepithelial cells of 11 and 15 day-old rat embryos were found to be interconnected near their luminal surface by extended junctional complexes, consisting of tight junctions and desmosome-like contacts. On the 11th and 12th embryonal day, small gap junction cell contacts occur in the juxtaluminal region of the neural tube. Besides these intercellular gap junctions, annulated gap junctions, located intracellularly, were also detected at this developmental stage. The latter type is thought to originate from intercellular gap junctions by an invagination process in the course of degradation of extended contacts which exist between neuroepithelial cells in earlier developmental phases. The decrease of gap junction number by the 14th and 15th embryonal day could be correlated with processes of cellular development and differentiation.
Animals↗
Synaptophysin and synaptoporin expression in the developing rat olfactory system.
The expressions of two closely related synaptic vesicle antigens synaptophysin and synaptoporin were examined in the olfactory system of the adult rat and during pre- and postnatal development. In the adult, immunocytochemistry showed that the continuously regenerating olfactory receptor neurons (primary neurons) produce both synaptophysin and synaptoporin which were localized in the cell bodies of the receptor neurons in the olfactory epithelium, their dendrites, axonal processes in the olfactory nerve and their terminals in the olfactory bulb glomeruli. Furthermore, ultrastructural analysis revealed synaptophysin- and synaptoporin-immunoreactivities associated with synaptic vesicles in most olfactory receptor axonal terminals impinging on dendrites of the mitral and tufted neurons (secondary neurons in the olfactory bulb circuitry) in the olfactory glomeruli. In like manner, tufted neurons, granule and periglomerular neurons (interneurons in the olfactory bulb circuitry) express both synaptophysin and synaptoporin. In contrast, mitral neurons expressed only the synaptophysin antigen which was likewise associated with mitral axonal terminals in their target the olfactory cortex. The patterns of synaptophysin and synaptoporin expressions in mitral neurons (synaptophysin only) and tufted neurons (synaptophysin and synaptoporin) were similar in prenatal, postnatal and adult rats as revealed by immunocytochemistry and in situ hybridization. However, the biosynthesis of synaptophysin and synaptoporin by granule and periglomerular neurons, olfactory bulb interneurons, occurred mainly postnatally.
Animals↗
Identification of a gene encoding a novel zinc finger protein in Saccharomyces cerevisiae.
In the course of a comprehensive genomic screen for cell cycle regulated genes in the yeast Saccharomyces cerevisiae (Price et al., 1991) we identified and characterized a transcriptional unit encoding a putative zinc finger protein named FZF1 (EMBL accession number: X67787). This gene encodes a protein containing five zinc fingers of the Cys2His2 class, three of which are positioned in tandem at the N-terminus. The fourth and fifth finger follow after an interruption of 61 and 66 amino acids, respectively. While FZF1 is constitutively expressed at a very low level, its deletion is not essential for growth. Its similarity with known transcription factors, however, suggests that the FZF1 gene product may serve as a transcription factor in yeast.
Amino Acid Sequence↗
Psychometric properties of a cognitive measure of personality disorders.
This study evaluated the internal consistency, 1-month test-retest reliability, and validity of a cognitive measure of personality disorders, the Belief Questionnaire (BQ; Beck, 1990). A large, nonclinical sample of college undergraduates completed the BQ, the MMPI-Personality Disorder scales (MMPI-PD; Morey, Waugh, & Blashfield, 1985), and the Personality Diagnostic Questionnaire-Revised (PDQ-R; Hyler & Rieder, 1987) at two times separated by 1 month. Results indicated high internal consistency and test-retest reliability for the BQ subscales. Validity results, however, were not so strong. The BQ scales were highly positively intercorrelated, and only moderate correspondence between BQ scores and corresponding scores from the MMPI-PD and PDQ-R was found.
Adolescent↗
Differentially regulated malate synthase genes participate in carbon and nitrogen metabolism of S. cerevisiae.
We have isolated a second gene (MLS1), which in addition to DAL7, encodes malate synthase from S. cerevisiae. Expression of the two genes is specific for their physiological roles in carbon and nitrogen metabolism. Expression of MLS1, which participates in the utilization of non-fermentable carbon sources, is sensitive to carbon catabolite repression, but nearly insensitive to nitrogen catabolite repression. DAL7, which participates in catabolism of the nitrogenous compound allantoin, is insensitive to carbon catabolite repression, but highly sensitive to nitrogen catabolite repression. Results obtained with null mutations in these genes suggest that S. cerevisiae contains at least one and perhaps two additional malate synthase genes.
Amidine-Lyases↗
DIT101 (CSD2, CAL1), a cell cycle-regulated yeast gene required for synthesis of chitin in cell walls and chitosan in spore walls.
A mutant screen has been designed to isolate mutants in Saccharomyces cerevisiae deficient in spore wall dityrosine. As shown by electron microscopy, most of the mutant spores lacked only the outermost, dityrosine-rich layer of the spore wall. Mutant dit101, however, was additionally lacking the chitosan layer of the spore wall. Chemical measurements showed that this mutant does not synthesize chitosan during sporulation. The mutant spores were viable but sensitive to lytic enzymes (glusulase or zymolyase). Unlike most of the dit-mutants, dit101 did show a distinctive phenotype in vegetative cells: they grew normally but contained very little chitin and were therefore resistant to the toxic chitin-binding dye, Calcofluor White. The cells showed barely detectable staining of the walls with Calcofluor White or primulin. The decrease in the amount of chitin in vegetative cells and the absence of chitosan in spores suggested that the mutant dit101 could be defective in a chitin synthase. Indeed, a genomic yeast clone harboring the gene, CSD2, sharing significant sequence similarity with yeast chitin synthases I and II (C. E. Bulawa (1992), Mol. Cell. Biol. 12, 1764-1776), complemented our mutant and was shown to correspond to the chromosomal locus of dit101. Thus, the mutations dit101 and csd2 (and probably also call; M. H. Valdivieso et al., (1991), J. Cell Biol. 114, 101-109) were shown to be allelic. The gene was mapped to chromosome II and was located about 3 kb distal of GAL1. Using this DNA clone, a transcript of about 3500-4000 nucleotides was detected. Comparing RNA isolated from vegetative cells and from sporulating cells at different times throughout the sporulation process, no significant differences in DIT101 transcript levels could be detected indicating absence of sporulation-specific transcriptional regulation. However, the amount of DIT101 transcript changed significantly at different stages of the mitotic cell cycle, peaking after septum formation, but before cytokinesis. As most of the chitin synthesis of vegetative cells occurs at this stage of the cell division cycle, chitin synthesis mediated by DIT101 could be primarily regulated at the level of transcription in vegetatively growing cells.
Cell Cycle↗
Meiotic chromosome condensation and pairing in Saccharomyces cerevisiae studied by chromosome painting.
Non-isotopic high resolution in situ hybridization was applied to cytological preparations of sporulating yeast cells. Ribosomal DNA (rDNA) and chromosome V-specific recombinant lambda clones were used to tag individual chromosomes and chromosome subregions. This allowed the study of chromosome behaviour during early meiotic prophase. It was found that chromatin becomes condensed and homologous DNA sequences then appear to become aligned prior to synaptonemal complex formation.
Chromosome Banding↗
Identification of a new set of cell cycle-regulatory genes that regulate S-phase transcription of histone genes in Saccharomyces cerevisiae.
Histone mRNA synthesis is tightly regulated to S phase of the yeast Saccharomyces cerevisiae cell cycle as a result of transcriptional and posttranscriptional controls. Moreover, histone gene transcription decreases rapidly if DNA replication is inhibited by hydroxyurea or if cells are arrested in G1 by the mating pheromone alpha-factor. To identify the transcriptional controls responsible for cycle-specific histone mRNA synthesis, we have developed a selection for mutations which disrupt this process. Using this approach, we have isolated five mutants (hpc1, hpc2, hpc3, hpc4, and hpc5) in which cell cycle regulation of histone gene transcription is altered. All of these mutations are recessive and belong to separate complementation groups. Of these, only one (hpc1) falls in one of the three complementation groups identified previously by other means (M. A. Osley and D. Lycan, Mol. Cell. Biol. 7:4204-4210, 1987), indicating that at least seven different genes are involved in the cell cycle-specific regulation of histone gene transcription. hpc4 is unique in that derepression occurs only in the presence of hydroxyurea but not alpha-factor, suggesting that at least one of the regulatory factors is specific to histone gene transcription after DNA replication is blocked. One of the hpc mutations (hpc2) suppresses delta insertion mutations in the HIS4 and LYS2 loci. This effect allowed the cloning and sequence analysis of HPC2, which encodes a 67.5-kDa, highly charged basic protein.
Amino Acid Sequence↗
[Morphometric-stereological study of hippocampal long term potentiation with special consideration of the analysis of variance with two-way hierarchical classification].
Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of vesicles in axo-spino-dendritic synapses of the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. Between the 3 groups (passive control, active control, LTP-group) we found no significant differences. Because of the great differences between the vesicles even within a single synapse we subsequently investigated the middle third of the molecular layer, i.e. the terminal area of the stimulated perforant path. No differences between the three groups we found here either. There was no confirmation for the expected greater homogenization of the synapses based on the uniform input. As a result of this study pure morphological studies without selective staining of specific population of synapses are considered inadvisable. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.
Analysis of Variance↗
A general approach to the isolation of cell cycle-regulated genes in the budding yeast, Saccharomyces cerevisiae.
We describe a general approach to the isolation of cell cycle-dependently regulated transcripts in Saccharomyces cerevisiae. This approach is based on the physical identification of cell cycle-regulated transcripts by Northern hybridization using as probes yeast DNA isolated from an ordered S. cerevisiae genomic library. The purpose of this is twofold; first, to assess the importance of transcriptional regulation in cell cycle control; and second, to identify novel genes that may have important roles in the eukaryotic cell cycle. We report the isolation of two previously uncharacterized genes that are transcribed at points in the cell cycle to which specific transcriptional activation has not been assigned: namely, mitosis and early G1 phase. It is argued that these transcripts serve as important landmarks for cell cycle events that are not readily distinguished by either morphological or cytological criteria. The cell cycle-dependent transcription of the RNR1 and CLN1 genes is also described and the implications for cell cycle control, in G1, are discussed with reference to these two genes.
Blotting, Northern↗