Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA preparations obtained from 122 species of fishes, 5 species of amphibians, and 13 species of reptiles were investigated in their compositional properties by analytical equilibrium centrifugation in CsCl density gradients. These species represented 21 orders of Osteichthyes, 3 orders of Chondrichthyes, 2 orders of amphibians, and 3 orders of reptiles. Modal buoyant densities of fish DNAs ranged from 1.696 to 1.707 g/cm3, the vast majority of values falling, however, between 1.699 and 1.704 g/cm3, which is the range covered by the DNAs of amphibians and reptiles. In all cases, DNA bands in CsCl were only weakly asymmetrical and only very rarely were accompanied by separate satellite bands (mostly on the GC-rich side). Intermolecular compositional heterogeneities were low in the vast majority of cases, and, like CsCl band asymmetries, at least partially due to cryptic or poorly resolved satellites. The present findings indicate, therefore, that DNAs from cold-blooded vertebrates are characterized by a number of common properties, namely a very wide spectrum of modal buoyant densities, low intermolecular compositional heterogeneities, low CsCl band asymmetries, and, in most cases, small amounts of satellite DNAs. In the case of fish DNAs a negative correlation was found between the GC level and the haploid size (c value) of the genome. If polyploidization is neglected, this phenomenon appears to be mainly due to the fact that increases and decreases in GC are associated with contraction and expansion phenomena, respectively, of intergenic noncoding sequences, which are GC poor relative to coding sequences.
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PMID:Compositional patterns in the nuclear genome of cold-blooded vertebrates. 212 75

The majority of models of radiation action developed over the past half century hold that the curvilinear dose responses exhibited by eukaryotic cells to sparsely ionizing radiations result from the interaction of pairs of lesions produced in sensitive targets of the cell. Within this conceptual framework, chromosomal exchange aberrations (e.g., interchanges) are believed to occur through the interaction of damaged sites on both chromosomes participating in the exchange. In contrast, the model proposed by Chadwick and Leenhouts (as well as some other models) suggests that such exchanges arise from initial radiation damage to only one chromosome, which then becomes associated with an undamaged chromosome. A particular aspect of this theory is that asymmetrical exchanges, such as dicentrics, may be formed from the rejoining of a broken end of one chromosome to the telomere of another. By using a DNA probe that specifically hybridizes to the telomeric region of human chromosomes, we were able to test this assertion directly. After scanning more than 200 dicentrics produced in normal human fibroblasts by 6 Gy of 60Co gamma rays, virtually none were found that contained telomeres located between the centromeres of this aberration type. Therefore, since the proposed telomere-break rejoining process, per se, is not necessarily a central element of the Chadwick-Leenhouts model, we suggest the theory be modified to exclude this mechanism.
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PMID:Telomere staining of human chromosomes and the mechanism of radiation-induced dicentric formation. 248 16

Fos and Jun proteins form a tight complex which binds specifically to the AP1 recognition sequence, a palindromic DNA element also referred to as the TPA responsive element (TRE). To elucidate the mechanism of Fos-Jun interaction with the TRE we have performed UV cross-linking studies using oligonucleotides where thymines were replaced with bromouracil. Our results indicate that both Fos and Jun directly contact the TRE but that the interaction of Fos and Jun with thymines in structurally equivalent positions in the two half sites of the TRE is different. In addition, we have carried out a comprehensive mutagenesis study of the TRE by introducing all possible point mutations plus thymine----uracil substitutions into the palindromic TRE core sequences and the adjacent nucleotides on both sides. The results of this analysis clearly show that the palindromic TRE is asymmetrical with respect to binding of Fos-Jun. We also show that a Fos protein complex with a homodimeric DNA binding site binds considerably less efficiently to TRE mutants with a perfect dyad symmetry compared with the binding to the wild-type TRE. This demonstrates that the asymmetrical recognition of the TRE is not due to the heterodimeric nature of the Fos/Jun complex but directly related to an asymmetry in the TRE sequence. The methyl groups of all four thymine residues within the TRE seem to be functionally crucial since thymine----uracil substitutions strongly reduce or abolish binding to Fos/Jun. The relevance of structurally equivalent methyl groups in the TRE core sequence is different, lending further support to the conclusion that the TRE is asymmetrical.
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PMID:Asymmetrical recognition of the palindromic AP1 binding site (TRE) by Fos protein complexes. 251 Oct 3

Twenty-two compounds related to camptothecin, a known inhibitor of eukaryotic topoisomerase I, were studied. The following effects on the actions of topoisomerase I were observed and were well correlated among most of the compounds studied: (a) inhibition of the first-order rate of relaxation of supercoiled DNA; (b) conversion of supercoiled DNA to nicked circles; and (c) single-strand cleavage of linear DNA at specific sites. The locations of the stimulated cleavage sites were the same for all of the active derivatives. Stereochemistry and the positions of substituents were found to be crucial for the presence or absence of effects on topoisomerase I, indicating that the compounds interact with an asymmetrical receptor site on the enzyme or enzyme-DNA complex. From the structure-activity relations, the regions of interaction between the camptothecin ring system and the receptor site were inferred. Striking correlations were observed between activity against topoisomerase I and reported activity against murine leukemias, indicating that an action on topoisomerase I is responsible for the antitumor activity of the camptothecins.
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PMID:Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. 253 27

The gene encoding diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) phosphorylase from yeast was isolated from a lambda gt11 library. The DNA sequence of the coding region was determined, and more than 90% of the deduced amino acid sequence was confirmed by peptide sequencing. The Ap4A phosphorylase gene (APA1) is unique in the yeast genome. Disruption experiments with this gene, first, supported the conclusion that, in vivo, Ap4A phosphorylase catabolizes the Ap4N nucleotides (where N is A, C, G, or U) and second, revealed the occurrence of a second Ap4A phosphorylase activity in yeast cells. Finally, evidence is provided that the APA1 gene product is responsible for most of the ADP sulfurylase activity in yeast extracts.
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PMID:Isolation, characterization, and inactivation of the APA1 gene encoding yeast diadenosine 5',5'''-P1,P4-tetraphosphate phosphorylase. 255 64

Complexes formed between Actinomycin D (ActD) and the tetranucleotides d(AGCT)2 and d(CGCG)2 were studied in detail by one and two-dimensional 1H and 31P NMR. The 31P two dimensional chemical exchange experiment, at room temperature on saturated complexes (1:1), showed unambiguously that the asymmetrical phenoxazone ring binds to the unique GC site under the two possible orientations in the d(AGCT)2 tetranucleotide but adopts a single orientation in the d(CGCG)2 tetranucleotide. For the d(CGCG)2:Act D saturated complex, complete assignments of all protons and phosphorus signals of the two-nucleotide strands, as well as of the two cyclic pentapeptide chains has allowed us to study in details the conformational features of the complex from NOE and coupling constants analysis. The tetranucleotide remains in a right-handed duplex, but the sugar puckers are modified for residues at the intercalation site. A uniform C2' endo pucker is observed for residues on the strand facing the quinoid side of the phenoxazone ring while a C2' endo-C3-endo equilibrium about 60% of C2' endo is proposed for the two residues on the strand facing the benzenoid side of the phenoxazone ring. In contrast to previous studies on ActD-DNA interactions, we have been able to measure the 3J phosphorus-proton coupling constants at the intercalation site but also adjacent to it, showing that 31P chemical shifts are not simply related to the backbone conformation. Molecular mechanics calculations, using empirical distances deduced from NOE effects as restrained distances during minimizations, led to a model differing mainly from those previously published by orientation of the N methyl groups of both N-Methyl-Valines.
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PMID:Reassessment of structural characteristics of the d(CGCG)2:actinomycin D complex from complete 1H and 31P NMR. 262 99

We report that pdxA, which is required for de novo biosynthesis of pyridoxine (vitamin B6) and pyridoxal phosphate, belongs to an unusual, multifunctional operon. The pdxA gene was cloned in the same 3.5-kilobase BamHI-EcoRI restriction fragment that contains ksgA, which encodes the 16S rRNA modification enzyme m6(2)A methyltransferase, and apaH, which encodes diadenosine tetraphosphatase (ApppA hydrolase). Previously, Blanchin-Roland et al. showed that ksgA and apaH form a complex operon (Mol. Gen. Genet. 205:515-522, 1986). The pdxA gene was located on recombinant plasmids by subcloning, complementation, and insertion mutagenesis, and chromosomal insertions at five positions upstream from ksgA inactivated pdxA function. DNA sequence analysis and minicell translation experiments demonstrated that pdxA encoded a 35.1-kilodalton polypeptide and that the stop codon of pdxA overlapped the start codon of ksgA by 2 nucleotides. The translational start codon of pdxA was tentatively assigned based on polypeptide size and on the presence of a unique sequence that was also found near the translational start of PdxB. This conserved sequence may play a role in translational control of certain pyridoxine biosynthetic genes. RNase T2 mapping of chromosomal transcripts confirmed that pdxA and ksgA were members of the same complex operon, yet about half of ksgA transcripts arose in vivo under some culture conditions from an internal promoter mapped near the end of pdxA. Transcript analysis further suggested that pdxA is not the first gene in the operon. These structural features support the idea that pyridoxine-biosynthetic genes are members of complex operons, perhaps to interweave coenzyme biosynthesis genetically with other metabolic processes. The results are also considered in terms of ksgA expression.
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PMID:Overlap between pdxA and ksgA in the complex pdxA-ksgA-apaG-apaH operon of Escherichia coli K-12. 267 Aug 94

Precise identification of centromeres is required for accurate scoring of asymmetrical chromosome aberrations, such as dicentrics. The centromeric regions of all human chromosomes can be labeled by in situ hybridization of a 30 nucleotide oligomer having the sequence of a conserved region of an alphoid DNA consensus sequence. Fluorescent detection of the hybridized probe allows rapid identification of centromeres and accurate scoring of dicentrics, multicentrics, acentric fragments, and the centromeric content of ring chromosomes. This procedure provides a novel approach for scoring these complex chromosome aberrations, particularly damage induced by radiation or radiomimetic agents.
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PMID:Labeling of human centromeres using an alphoid DNA consensus sequence: application to the scoring of chromosome aberrations. 273 20

Bacterial DNA-methylases with known recognition sites (RS) were used as probes for structural-and-functional analysis of eukaryotic genome. Adenine and cytosine DNA-methylases recognizing 4 to 6-member unique and degenerative nucleotide sequences having a symmetrical and asymmetrical structure were used for probing. The use of a set of methylases enabled the selection of a probe that was the most sensitive for the given pathology. Thus, severe hypothyrosis was found to be associated with changes in the acceptor capacity of liver DNA in the heterologous++ methylation reaction as could be evidenced from testing by two probes, CCCC and GAATGC. In the cells of chicken liver hepatoma MC29, the acceptor capacity of DNA during GGA methylation appeared to be altered in the greatest degree. DNA-methylases with degenerative SR are weakly specific probes for the study of structural changes (methylation) of the animal genome.
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PMID:[Use of bacterial DNA-methylases for structuro-functional analysis of the eukaryotic genome]. 275 68

The genomic domain of about 20 kbp of the chicken alpha-type globin genes, framed by AT-rich linkers (ATRLs; Moreau et al. 1982) and repetitive sequences (Broders et al. 1986), was cut into 13 fragments and subcloned. The in vitro labelled individual restriction fragments were used to test the extent of the transcribed domain by blot-hybridization of nuclear RNA in large excess from normal adult chicken and Avian Erythroblastosis Virus (AEV)-transformed erythroblasts. In both these types of cells, the AT-rich segments situated 6 kbp upstream of the first gene as well as all the domain including the embryonic pi and the adult alpha D and alpha A genes down to the AT-rich segment placed 3 kbp downstream were found to be transcribed. Electrophoresis of nuclear RNA, Northern blotting and hybridization with most of the nick-translated DNA probes revealed in all cases the presence of heterogeneous globin RNA molecules in the 3-12 kb range, as well as some distinct RNA bands. Single-stranded RNA probes of some genomic segments indicated asymmetrical transcription of the minus strand. A 12 kb globin-specific RNA including the pi and alpha A genes but not the intervening alpha D gene was observed in AEV-transformed cells: it includes sequences located far upstream and downstream from the alpha globin genes and might represent a processing product of a full length transcript spanning the whole domain. Reverse transcription by extension of primers placed in the first exon of each of the three globin genes confirmed the presence of continuous transcripts of the domain including the two adult and the embryonic globin genes.
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PMID:Transcription of the alpha globin gene domain in normal and AEV-transformed chicken erythroblasts: mapping of giant globin-specific RNA including embryonic and adult genes. 282 73


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