Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the yeast Saccharomyces cerevisiae, circular or linear plasmids containing a functional centromere (CEN) and a chromosomal replicator (ARS) are mitotically stable and segregate as ordinary yeast chromosomes in the first and second meiotic divisions. A centromere in S. cerevisiae consists of a region of DNA, approximately 150 bp in length, containing three important sequence elements, which are folded with proteins into a specific conformation in the chromatin (the yeast kinetochore). Each of the functional CEN sequences contains a high (91% to 95%) AT region (element II), 78 to 86 bp in length, flanked on one side by the common sequence PuTCACPuTG (element I), and on the other by the sequence TGTTT.TG.TTTCCGAAA....AAA (element III). Deletions in the element II region partially inactivate mitotic function and cause precocious separation of the sister chromatids in meiosis I. Element III appears to be a protein binding site, as evidenced by the following observations. Various point mutations in element III inactivate centromere function, especially in the central CCG (17). One or more protein binding sites in the element III region can be demonstrated by an exonuclease III blocking assay. Wild-type CEN sequences compete strongly in this binding assay, whereas certain functionally inactive mutant CEN sequences do not. In addition, various DNA segments containing either CEN3 or the element III region strongly repress expression of the yeast GAL1 gene when inserted immediately upstream from the transcriptional start site. Helical DNA segments containing CEN3 or CEN14 are shown to be bent or distorted in shape in the high-AT element II region.
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PMID:Structural studies on centromeres in the yeast Saccharomyces cerevisiae. 303 43

An evolutionarily ancient mechanism is used for intracellular membrane fusion events ranging from endoplasmic reticulum-Golgi traffic in yeast to synaptic vesicle exocytosis in the human brain. At the heart of this mechanism is the core complex of N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAPs), and SNAP receptors (SNAREs). Although these proteins are accepted as key players in vesicular traffic, their molecular mechanisms of action remain unclear. To illuminate important structure-function relationships in NSF, a screen for dominant negative mutants of yeast NSF (Sec18p) was undertaken. This involved random mutagenesis of a GAL1-regulated SEC18 yeast expression plasmid. Several dominant negative alleles were identified on the basis of galactose-inducible growth arrest, of which one, sec18-109, was characterized in detail. The sec18-109 phenotype (abnormal membrane trafficking through the biosynthetic pathway, accumulation of a membranous tubular network, growth suppression, increased cell density) is due to a single A-G substitution in SEC18 resulting in a missense mutation in Sec18p (Thr(394)-->Pro). Thr(394) is conserved in most AAA proteins and indeed forms part of the minimal AAA consensus sequence that serves as a signature of this large protein family. Analysis of recombinant Sec18-109p indicates that the mutation does not prevent hexamerization or interaction with yeast alpha-SNAP (Sec17p), but instead results in undetectable ATPase activity that cannot be stimulated by Sec17p. This suggests a role for the AAA protein consensus sequence in regulating ATP hydrolysis. Furthermore, this approach of screening for dominant negative mutants in yeast can be applied to other conserved proteins so as to highlight important functional domains in their mammalian counterparts.
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PMID:A screen for dominant negative mutants of SEC18 reveals a role for the AAA protein consensus sequence in ATP hydrolysis. 1074 34