DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Cell Line: Established cell cultures that have the potential to propagate indefinitely.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Bacterial Proteins: Proteins found in any species of bacterium.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Viral Proteins: Proteins found in any species of virus.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Kinetics: The rate dynamics in chemical or physical systems.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Genes, Bacterial: The functional hereditary units of BACTERIA.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Fungal Proteins: Proteins found in any species of fungus.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Operon: In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Chenopodium quinoa: A species of the Chenopodium genus which is the source of edible seed called quinoa. It contains makisterone A and other STEROIDS, some having ECDYSTEROID activity on insects.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Electrophoretic Mobility Shift Assay: An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Protein Sorting Signals: Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Lysine: An essential amino acid. It is often added to animal feed.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Genes, Viral: The functional hereditary units of VIRUSES.Chloramphenicol O-Acetyltransferase: An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Structural Homology, Protein: The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Sasa: A plant genus of the family POACEAE. Folin is the water-soluble extract from Sasa albomarginata. Sasa kurinensis is an ingredient of Sho-ju-sen, a Japanese herbal medicine.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Sp1 Transcription Factor: Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Chromosome Deletion: Actual loss of portion of a chromosome.5' Untranslated Regions: The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Histidine: An essential amino acid that is required for the production of HISTAMINE.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Genes, Fungal: The functional hereditary units of FUNGI.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.RNA Precursors: RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.Arginine: An essential amino acid that is physiologically active in the L-form.Acid Anhydride Hydrolases: A group of enzymes that catalyze the hydrolysis of diphosphate bonds in compounds such as nucleoside di- and tri-phosphates, and sulfonyl-containing anhydrides such as adenylylsulfate. (Enzyme Nomenclature, 1992) EC 3.6.beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.DNA Replication: The process by which a DNA molecule is duplicated.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Bacillus subtilis: A species of gram-positive bacteria that is a common soil and water saprophyte.Protein Interaction Domains and Motifs: Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.Leucine: An essential branched-chain amino acid important for hemoglobin formation.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Nuclear Localization Signals: Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at the NUCLEAR PORE.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Methanococcaceae: A family of anaerobic METHANOCOCCALES whose organisms are motile by means of flagella. These methanogens use carbon dioxide as an electron acceptor.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.TATA Box: A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.Artificial Gene Fusion: The in vitro fusion of GENES by RECOMBINANT DNA techniques to analyze protein behavior or GENE EXPRESSION REGULATION, or to merge protein functions for specific medical or industrial uses.Oncogene Proteins, Viral: Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Luciferases: Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesGenes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.DNA-Directed RNA Polymerases: Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).Genes, Regulator: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.RNA, Bacterial: Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.Viral Nonstructural Proteins: Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.PhosphoproteinsDNA Footprinting: A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Helix-Turn-Helix Motifs: The first DNA-binding protein motif to be recognized. Helix-turn-helix motifs were originally identified in bacterial proteins but have since been found in hundreds of DNA-BINDING PROTEINS from both eukaryotes and prokaryotes. They are constructed from two alpha helices connected by a short extended chain of amino acids, which constitute the "turn." The two helices are held at a fixed angle, primarily through interactions between the two helices. (From Alberts et al., Molecular Biology of the Cell, 3d ed, p408-9)Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Tobacco: A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Zinc: A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Bacteriophage T4: Virulent bacteriophage and type species of the genus T4-like phages, in the family MYOVIRIDAE. It infects E. coli and is the best known of the T-even phages. Its virion contains linear double-stranded DNA, terminally redundant and circularly permuted.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.Leucine Zippers: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.Polyproteins: Proteins which are synthesized as a single polymer and then cleaved into several distinct proteins.RNA Replicase: An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293)RNA Helicases: A family of proteins that promote unwinding of RNA during splicing and translation.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Amino Acids, Acidic: Amino acids with side chains that are negatively charged at physiological pH.RNA, Small Nuclear: Short chains of RNA (100-300 nucleotides long) that are abundant in the nucleus and usually complexed with proteins in snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR). Many function in the processing of messenger RNA precursors. Others, the snoRNAs (RNA, SMALL NUCLEOLAR), are involved with the processing of ribosomal RNA precursors.

Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma. (1/15602)

The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC.  (+info)

Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor. (2/15602)

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective lysosome-related organelles. Here, we report the identification of two HPS patients with mutations in the beta 3A subunit of the heterotetrameric AP-3 complex. The patients' fibroblasts exhibit drastically reduced levels of AP-3 due to enhanced degradation of mutant beta 3A. The AP-3 deficiency results in increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and lamp-2, but not of nonlysosomal proteins. These differential effects are consistent with the preferential interaction of the AP-3 mu 3A subunit with tyrosine-based signals involved in lysosomal targeting. Our results suggest that AP-3 functions in protein sorting to lysosomes and provide an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery.  (+info)

p53 status of newly established acute myeloid leukaemia cell lines. (3/15602)

We analysed the status of the p53 gene and protein in eight newly established acute myeloid leukaemia (AML) cell lines representing blast cells of either de novo leukaemia patients in first remission or patients with relapsed and chemotherapy-resistant disease causing their death. There were no mutations in the p53 gene in any of the cell lines as analysed by single-strand conformation polymorphism of amplified exons 5-8. However, the p53 protein was clearly and consistently expressed in all of these cell lines, as shown by immunohistochemistry, Western blotting and flow cytometry. The consistently expressed p53 protein was located in both the nucleus and the cytoplasm of all the cell lines and, as shown by flow cytometry, it was mostly in a conformation typical of the mutated protein. These AML cell lines offer a tool for studying the production and function of the p53 protein and its possible role in cell cycle regulation and chemoresistance as well as in the regulation of apoptosis in AML.  (+info)

Genomic structure and alterations of homeobox gene CDX2 in colorectal carcinomas. (4/15602)

Expression of CDX2, a caudal-related homeobox gene, was found to be decreased in colorectal carcinomas. Heterozygous null mutant mice as to Cdx2 develop multiple intestinal adenomatous polyps. To clarify the role of CDX2 in colorectal carcinogenesis, we determined its genomic structure, and searched for mutations of CDX2 in 49 sporadic colorectal carcinomas and ten hereditary non-polyposis colorectal cancers (HNPCC) without microsatellite instability. None of them exhibited a mutation. We further examined 19 HNPCC carcinomas with microsatellite instability for mutations in a (G)7 repeat site within CDX2. One of them (5.3%) exhibited one G insertion. Loss of heterozygosity was observed in 2 of the 20 (10%) informative sporadic carcinomas, and in one of the three (33.3%) informative HNPCC cancers. These data indicate that CDX2 may play only a minor role in colorectal carcinogenesis.  (+info)

Analysis of TSG101 tumour susceptibility gene transcripts in cervical and endometrial cancers. (5/15602)

Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent studies have localized the TSG101 gene in this region, and also demonstrated a high frequency of abnormalities of this gene in human breast cancer. To determine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endometrial carcinoma, as well as nearby non-cancerous tissue from the same patients, and 16 blood samples from healthy persons as normal control were analysed by Southern blot analysis of genomic DNA, reverse transcription of the TSG101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in cancerous or non-cancerous tissues of the uterus and cervix and in normal peripheral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and no definite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-cancerous tissue, normal peripheral mononuclear cells also had abnormal transcripts. Given these findings, the role of the TSG101 gene as a tumour-suppressor gene should be re-evaluated. Because some aberrant transcripts could be found at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products.  (+info)

Microsatellite instability, Epstein-Barr virus, mutation of type II transforming growth factor beta receptor and BAX in gastric carcinomas in Hong Kong Chinese. (6/15602)

Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is found in a proportion of gastric carcinomas. Little is known of the links between MI and Epstein-Barr virus (EBV) status and clinicopathological elements. Examination of genes mutated through the MI mechanism could also be expected to reveal important information on the carcinogenic pathway. Seventy-nine gastric carcinomas (61 EBV negative, 18 EBV positive) from local Hong Kong Chinese population, an intermediate-incidence area, were examined. Eight microsatellite loci, inclusive of the A10 tract of type II transforming growth factor beta receptor (TbetaR-II), were used to evaluate the MI status. MI in the BAX and insulin-like growth factor II receptor (IGF-IIR) genes were also examined. High-level MI (>40% unstable loci) was detected in ten cases (12.7%) and low-level MI (1-40% unstable loci) in three (3.8%). High-level MI was detected in two EBV-associated cases (11%) and the incidence was similar for the EBV-negative cases (13%). The high-level MIs were significantly associated with intestinal-type tumours (P = 0.03) and a more prominent lymphoid infiltrate (P = 0.04). Similar associations were noted in the EBV-positive carcinomas. The high-level MIs were more commonly located in the antrum, whereas the EBV-associated carcinomas were mostly located in body. Thirteen cardia cases were negative for both high-level MI and EBV. All patients aged below 55 were MI negative (P = 0.049). Of the high-level MIs, 80% had mutation in TbetaR-II, 40% in BAX and 0% in IGF-IIR. Of low-level MIs, 33% also had TbetaR-II mutation. These mutations were absent in the MI-negative cases. Of three lymphoepithelioma-like carcinomas, two cases were EBV positive and MI negative, one case was EBV negative but with high-level MI. In conclusion, high-level MIs were present regardless of the EBV status, and were found in a particular clinicopathological subset of gastric carcinoma patient. Inactivation of important growth regulatory genes observed in these carcinomas confirms the importance of MI in carcinogenesis.  (+info)

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma. (7/15602)

p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12-30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alpha-fetoprotein levels and clinicopathological characteristics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P<0.03 and P<0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative 'good prognosis' in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis.  (+info)

Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. (8/15602)

Endocrine pancreatic tumors (EPT) and neuroendocrine tumors (NET) occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). We analyzed the frequency of allelic deletions and mutations of the recently identified MEN1 gene in 53 sporadic tumors including 30 EPT and 23 NET (carcinoids) of different locations and types. Allelic deletion of the MEN1 locus was identified in 18/49 (36.7%) tumors (13/30, 43.3% in EPT and 5/19, 26.3% in NET) and mutations of the MEN1 gene were present in 8/52 (15.3%) tumors (4/30 (13.3%) EPT and 4/22 (18.1%) NET). The somatic mutations were clustered in the 5' region of the coding sequence and most frequently encompassed missense mutations. All tumors with mutations exhibited a loss of the other allele and a wild-type sequence of the MEN1 gene in nontumorous DNA. In one additional patient with a NET of the lung and no clinical signs or history of MEN1, a 5178-9G-->A splice donor site mutation in intron 4 was identified in both the tumor and blood DNA, indicating the presence of a thus far unknown MEN1 syndrome. In most tumor groups the frequency of allelic deletions at 11q13 was 2 to 3 times higher than the frequency of identified MEN1 gene mutations. Some tumor types, including rare forms of EPT and NET of the duodenum and small intestine, exhibited mutations more frequently than other types. Furthermore, somatic mutations were not restricted to foregut tumors but were also detectable in a midgut tumor (15.2% versus 16.6%). Our data indicate that somatic MEN1 gene mutations contribute to a subset of sporadic EPT and NET, including midgut tumors. Because the frequency of mutations varies significantly among the investigated tumor subgroups and allelic deletions are 2 to 3 times more frequently observed, factors other than MEN1 gene inactivation, including other tumor-suppressor genes on 11q13, may also be involved in the tumorigenesis of these neoplasms.  (+info)

  • Our broad analysis demonstrates that the qBiomarker's performance is on par with that of other labour-intensive and expensive methods of cancer mutation detection of frequently altered cancer-associated genes, and provides a foundation for supporting its consideration as an option for molecular diagnostics. (nature.com)
  • Mutational analysis of NPHS2 and WT1 genes in Saudi children with nephrotic syndrome. (alliedacademies.org)
  • Up to date, several causative genes related to NS have been identified by either using direct DNA sequencing approaches or next-generation sequencing technology [ 6 - 12 ]. (alliedacademies.org)
  • We used array comparative genomic hybridization, mutational profiling to assess the status of specific genes, mRNA expression profiling, and immunohistochemical analyses of proteins implicated in thymic tumor pathogenesis. (aacrjournals.org)
  • In this study, molecular genetic analysis was performed on all these 12 genes in 25 Chinese families with congenital cataract. (molvis.org)
  • The establishment of the mutational spectrum for NDMA in endogenous mammalian genes is necessary if exposure to NDMA, based on its mutational specificity, is going to be assessed in human tissues. (epa.gov)
  • The results of this analysis seem to indicate that positive selection for gain-of-function in tumor suppressor genes is an important aspect of tumorigenesis, blurring the distinction between tumor suppressors and oncogenes. (pubmedcentralcanada.ca)
  • DNA phosphorothioation, conferred by dnd genes, was originally discovered in the soil-dwelling bacterium Streptomyces lividans , and thereafter found to exist in various bacterial genera. (frontiersin.org)
  • RNA-seq experiments revealed that, catalase and organic hydroperoxide resistance gene expression were not up-regulated in the wild type strain, suggesting that the resistance to oxidative stress was not due to the up-regulation of these genes by DNA phosphorothioation. (frontiersin.org)
  • Quantitative RT-PCR analysis was conducted to trace the expression of the catalase and the organic hydroperoxide resistance genes after peroxides treatments. (frontiersin.org)
  • In summary, exome-wide analysis of the mutational landscape of aGCT revealed that, except for the TERT promoter mutation, recurrence and/or aggressive behavior is not defined by activation or loss of specific genes. (aacrjournals.org)
  • The entire coding sequences of the SLC3A1 and SLC7A9 genes were analysed by means of SSCA and DNA sequencing in 53 cystinuria patients and genetic findings were related to urinary excretion of cystine and dibasic amino acids in a subset of the patient group. (diva-portal.org)
  • Here we describe the clinical application of MiSeq, a next-generation sequencing platform to screen mutational hotspots in 54 cancer-related genes including genes relevant in acute myeloid leukemia ( NRAS , KRAS , FLT3 , NPM1 , DNMT3A , IDH1/2 , JAK2 , KIT and EZH2 ). (haematologica.org)
  • However, because the protein coding capacity of mitochondrial DNA (mtDNA) is limited to 13 respiratory subunits, nuclear genes must provide the vast majority of products required for mitochondrial oxidative functions and biosynthetic capacity. (asm.org)
  • In addition, nuclear genes must play a predominant role in controlling mitochondrial transcription, translation, and DNA replication. (asm.org)
  • In this retrospective study, we performed polymerase chain reaction (PCR) amplification and deoxyribonucleic acid (DNA) sequencing of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in 20 FFPE (formalin-fixed, paraffin-embedded) and 5 frozen GIST samples. (isciii.es)
  • The studies seek to identify the signal transduction pathways, specific DNA elements and transcription factors which are required for the tissue-specific, regulated expression of these pituitary hormone genes. (ohsu.edu)
  • We hypothesize that unlike Dnmt3a, Dnmt3b does not oligomerize and to test this hypothesis, we performed mutational analysis of the conserved residues in Dnmt3b that are critical for Dnmt3a tetrameric structure. (purdue.edu)
  • Crystal structure analysis of an Escherichia coli homologue identified conserved amino acid residues that are critical for its substrate recognition/interaction and base hydrolysis functions. (uzh.ch)
  • On the basis of amino acid sequence alignments and structural data of related enzymes, we have performed a mutational analysis of 14 amino acid residues in the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase. (cf.ac.uk)
  • The target residues are located within the ten conserved amino acid sequence motifs characteristic for cytosine-C5 methyltransferases and in the putative DNA recognition domain of the enzyme (TRD). (cf.ac.uk)
  • Characterization of these mutants, by in vitro/in vivo restriction assays and DNA/AdoMet binding studies, indicated that most of the residues present in the AdoMet-binding pocket were not absolutely essential. (unthsc.edu)
  • Sankpal, UT & Rao, DN 2002, ' Mutational analysis of conserved residues in Hhal DNA methyltransferase ', Nucleic Acids Research , vol. 30, no. 12, pp. 2628-2638. (unthsc.edu)
  • This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. (frontiersin.org)
  • Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, initiating the base excision repair pathway. (ebi.ac.uk)
  • The Cre/loxP system has been used in transgenic models primarily to excise DNA flanked by loxP sites for gene deletion. (nih.gov)
  • Reporter gene expression analysis, electrophoretic mobility shift assays and chromatin immunoprecipitation studies were utilized to examine the functional effects of the deletion. (arctichealth.org)
  • DNA methylation is an epigenetic process involved in gene regulation that is key for cell differentiation and viability. (purdue.edu)
  • To determine the role of Acr-DNA adducts in p53 mutagenesis in CS-related lung cancer we mapped the distribution of Acr-DNA adducts at the sequence level in the p53 gene of lung cells using the UvrABC incision method in combination with ligation-mediated PCR. (pnas.org)
  • The tumor suppressor gene p53 is frequently mutated in human cancers ( 1 , 2 ), and its mutational patterns often bear the fingerprints of the etiological carcinogens. (pnas.org)
  • This assay is also available as PCR-based pyrosequencing of DNA to examine codons 595 to 600 from exon 15 (the most common mutation site) and codons 468 to 474 from exon 11 of the BRAF gene. (mdanderson.org)
  • Mutational analysis of the HvDWARF gene with the "reverse genetics" approach allowed for its detailed functional analysis at the level of protein functional domains. (mdpi.com)
  • This assay is available as PCR-based DNA pyrosequencing for codons 338 in exon 2 of the CXCR4 gene. (mdanderson.org)
  • In addition to their role in base excision repair, DNA glycosylase enzymes have been implicated in the repression of gene silencing in A. thaliana, N. tabacum and other plants by active demethylation. (wikipedia.org)
  • In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. (scielo.br)
  • In some cases, to test the effect of different variables on mutational analysis by SSCP, we selected samples known to harbor single nucleotide changes in the human insulin receptor (HIR) gene, in the adenomatous polyposis coli (APC) gene, and in the mismatch repair gene hMLH1 (11-13). (thefreedictionary.com)
  • Although much is known about how patterns of gene mutation are affected by small-scale structures-such as the groups of three bases called trinucleotides-or by the large-scale "compartments" into which DNA is organized in the nucleus, relatively little is known about the effects of "mesoscale" DNA structures that may extend 30 base pairs around the site of a mutation. (genengnews.com)
  • The MT-TL1 gene provides instructions for making a molecule called a transfer RNA (tRNA), which is a chemical cousin of DNA. (medlineplus.gov)
  • Next, the researchers compared these data with clinical data from longitudinal studies and gene expression analyses. (medicalnewstoday.com)
  • A comprehensive analysis using single-gene assays requires large amounts of DNA, is cumbersome and timely consolidation of results for clinical reporting is challenging. (haematologica.org)
  • Functional analyses by using a dual-luciferase reporter assay system showed that the mutant TBX20 lost the ability to transactivate the target gene ANF . (medsci.org)
  • Identification of a poxvirus gene encoding a uracil DNA glycosylase. (ebi.ac.uk)
  • Previously we demonstrated that DNA adducts induced by diol epoxides of polycyclic aromatic hydrocarbons (PAHs), a major category of cigarette smoke (CS) carcinogens, preferentially occur at p53 mutational hotspots in CS-related lung cancers and that adducts formed at these locations are poorly repaired ( 5 - 7 ). (pnas.org)
  • Here we apply three independent tests, accounting for non-uniform base compositions in synonymous and non-synonymous sites, to test whether the hotspots emerge via selection or due to mutational bias. (pubmedcentralcanada.ca)
  • The presence of hotspots is compatible with either a mutational or a selectional scenario or a combination thereof [ 14 , 17 ]. (pubmedcentralcanada.ca)
  • Previous investigation by others into breast cancer mutation hotspots associated with APOBEC enzymes identified DNA palindromes, features in which a specific sequence on one side of a mutation is repeated in reverse on the other side, suggesting the stem-loop hairpin structure. (genengnews.com)
  • LigA drives the process of the ligation by wrapping its protein clamp around the DNA and creating large protein conformational changes and remodeling of the active site. (wikipedia.org)
  • The p53 protein is called "the guardian of the genome" because this multifunctional transcription factor, which regulates cell cycle progression, repair and programmed cell death in mammals, targets for apoptosis those cells that accumulate unsustainable DNA damage [ 1 - 4 ]. (pubmedcentralcanada.ca)
  • Mutagenesis of region 4 of sigma 28 from Chlamydia trachomatis defines determinants for protein-protein and protein-DNA interactions. (semanticscholar.org)
  • Although a number of studies have characterized the DNA binding properties of the WT1 protein, recent evidence has suggested that WT1 may also have a role in RNA metabolism. (mendeley.com)
  • A) Ability of two putative Nkx-2.5 binding sites, N2 and N3, to form protein-DNA complexes with nuclear extracts from Nkx-2.5-transfected cells. (asm.org)
  • Analysis of the role of the mitogen-activated protein kinase in mediating cyclic-adenosine 3′,5′-Monophosphate effects on prolactin promoter activity. (ohsu.edu)
  • Characterization of DNA regions mediating the ability of Ca2+/calmodulin dependent protein kinase II to stimulate prolactin promoter activity. (ohsu.edu)
  • Here, we constructed a panel of APOBEC3G amino acid substitution mutants and performed a series of biochemical, genetic, and structural assays to distinguish between "Brim" and "Kink" models for single-strand DNA binding. (mdpi.com)
  • As a contribution to a better understanding of the developmental processes that are specific to plants, we have begun a genetic analysis of leaf ontogeny in the model system Arabidopsis thaliana by performing a large-scale screening for mutants with abnormal leaves. (genetics.org)
  • As a contribution to the causal analysis of plant leaf development, we first performed a large-scale screen for EMS-induced mutants with aberrantly shaped or sized leaves. (genetics.org)
  • Sequence analysis of the URA3 mutants revealed approximately 48% frameshifts, approximately 44% base substitutions and approximately 8% complex events. (biomedsearch.com)
  • In the present study, the identification of the HvDWARF genomic sequence, its mutational and functional analysis and characterization of new mutants are reported. (mdpi.com)
  • Analysis of their impact on phenotype of the mutants was performed. (mdpi.com)
  • In this study, we have analyzed the crystal structures, DNA binding and the response to ATP binding of three Glu38 mutants. (rcsb.org)
  • To determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1-like syndrome (NFLS) in a large cohort of patients. (nih.gov)
  • In a second cross-sectional study, 1318 unrelated anonymous samples collected in 2003-2007 from patients with a broad range of signs typically found in neurofibromatosis type 1 (NF1) but no detectable NF1 germline mutation underwent SPRED1 mutation analysis. (nih.gov)
  • Using 32 P-postlabeling/PAGE and authentic standards, we identified dA-aristolactam (AL) and dG-AL DNA adducts in the renal cortex of patients with EN but not in patients with other chronic renal diseases. (pnas.org)
  • Methods: Mutation analysis was accomplished by direct sequencing of the complete 8 exons of NPHS2 and exons 8 and 9 of WT1 in 20 patients with steroid-resistant nephrotic syndrome, 25 with steroid-dependent nephrotic syndrome, and 13 with frequently-relapse nephrotic syndrome. (alliedacademies.org)
  • This pathology has nuclear heterogeneous genetic origins, and at present, molecular diagnostic tests on nuclear DNA cover only 30% of BrS patients. (cdc.gov)
  • Mutational analysis of patients with X-linked adrenoleukodystrophy. (nih.gov)
  • For the case-control analysis of OGG1 R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. (springer.com)
  • The accuracy of plasma RAS mutational status determined by OncoBEAM RAS kit was confirmed for Japanese mCRC patients. (oncoletter.ch)
  • The concordance rate between plasma- and tissue-based analyses was 86.4% in overall, rising to 89.2% in patients excluding lung metastasis alone, with 13.6% of discordant cases being potentially attributed to variables of tissue heterogeneity, a longer interval in sample collection from archived tissue to plasma and a lower amount of ctDNA shed into plasma. (oncoletter.ch)
  • this study analyses the impact of using an NGS platform for molecular diagnosis of mCRC patients. (oncoletter.ch)
  • KRAS mutational status ranks among one of the most important scientific advances in colorectal cancer and has the potential to redefine how these patients are currently treated. (thefreedictionary.com)
  • There's growing interest in our molecular diagnostic tests by hematology-oncology specialists, particularly for the cell-free detection and monitoring of mutational status in patients with histiocytic diseases, as well as other hematologic malignancies that harbor the BRAF V600E mutation," said Mark Erlander, Ph. (thefreedictionary.com)
  • There was "strong positive correlation" between a new mutational signature called signature 32 and the duration of the treatment with azathioprine in immunosuppressed patients. (medicalnewstoday.com)
  • The mutational signatures are specific and therapy-related, as they are only present in the genomes of relapsed ALL patients but not in other pediatric or adult cancer genomes," Zhang said. (newswise.com)
  • The analysis also included targeted deep sequencing of leukemic cells collected regularly during treatment of 16 patients. (newswise.com)
  • APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. (mdpi.com)
  • Nicks allow for the much-needed release of torsion in the strand during DNA replication. (wikipedia.org)
  • Some sources of mismatched base pairs include replication errors and deamination of 5-methylcytosine DNA to form thymine. (wikipedia.org)
  • For eukaryotes specifically, the mechanism of DNA replication elongation between the leading and lagging strand differs. (wikipedia.org)
  • Uracil DNA glycosylases remove uracil from DNA, which can arise either by spontaneous deamination of cytosine or by the misincorporation of dU opposite dA during DNA replication. (wikipedia.org)
  • Moreover, 100-200 nucleotides of the telomeric DNA are removed from both ends of chromosomes with each round of replication, perhaps due to the action of a 5′-3′ exonuclease ( 9 ). (aacrjournals.org)
  • LANA binds the terminal repeats via the C-terminal DNA-binding domain (DBD) to support latent DNA replication. (bcm.edu)
  • In summary, these data suggest that the secondary and tertiary structures of LANA and EBNA1 DBDs are conserved and are critical for (i) sequence-specific DNA binding, (ii) multimer formation, (iii) LANA-dependent transcriptional repression, and (iv) DNA replication. (bcm.edu)
  • Although NAs can effectively suppress HBV replication by suppressing the activity of viral reverse transcriptase, these drugs alone have little or no ability to eliminate replicative HBV templates, i.e., covalently closed circular DNA (cccDNA) [ 4 , 5 ]. (ijbs.com)
  • Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. (ovid.com)
  • Sensitive tumour detection and classification using plasma cell-free DNA methylomes. (sickkids.ca)
  • This project will evaluate if ctDNA can be utilised for tumour genome characterisation and disease detection to guide treatment decisions with an ultimate objective to incorporate ctDNA analysis as a routine diagnostic modality for MM. (monash.edu)
  • Furthermore, we found that Acr can greatly reduce the DNA repair capacity for damage induced by benzo[ a ]pyrene diol epoxide. (pnas.org)
  • Together these results suggest that Acr is a major etiological agent for CS-related lung cancer and that it contributes to lung carcinogenesis through two detrimental effects: DNA damage and inhibition of DNA repair. (pnas.org)
  • PAHs have been shown to be strong carcinogens, and thus PAH-induced DNA damage may shape the p53 mutational pattern in lung cancer and may also represent a strong molecular link between lung cancer and cigarette smoking ( 1 , 2 , 5 - 7 ). (pnas.org)
  • In this study, we report for the first time that a proportion of human lung cancer cell lines did not properly arrest before entering mitosis in the presence of a catalytic, circular cramp-forming topoisomerase II inhibitor ICRF-193, whereas the decatenation G 2 checkpoint impairment was present independently of the impaired DNA damage G 2 checkpoint. (aacrjournals.org)
  • (11) previously reported that in contrast to DNA damage checkpoint, decatenation G 2 checkpoint activation relies on ataxia telangiectasia and Rad3-related (ATR) activity and nuclear exclusion of cyclin B1 instead of ataxia-telangiectasia mutated (ATM)-dependent down-regulation of cdc2/cyclin B1 activity. (aacrjournals.org)
  • A nick is a discontinuity in a double stranded DNA molecule where there is no phosphodiester bond between adjacent nucleotides of one strand typically through damage or enzyme action. (wikipedia.org)
  • Nicked DNA can be the result of DNA damage or purposeful and carefully regulated biomolecular reactions carried out in the cell. (wikipedia.org)
  • Independent of replicative age, factors such as oncogenic activation, DNA damage, chromatin remodeling, cellular stress, overexpression of cyclin-dependent kinase (Cdk) inhibitors, and deprotection of chromosome ends can also induce a phenotype resembling senescence ( 11 -16 ). (aacrjournals.org)
  • For instance, some mutational signatures are associated with age, others with DNA damage, and others yet with tobacco smoking or ultraviolet light exposure. (medicalnewstoday.com)
  • Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas. (biomedcentral.com)
  • Ligases are versatile and ubiquitous enzymes that join the 3' hydroxyl and 5' phosphate ends to form a phosphodiester bond, making them essential in nicked DNA repair, and ultimately genome fidelity. (wikipedia.org)
  • DNA mismatch repair (MMR) is an important DNA repair system that helps maintain genome plasticity by correcting mismatches, or non Watson-Crick base pairs in the a DNA duplex. (wikipedia.org)
  • Based on the sequence alignment of promoters recognized by FliA and genome in silico analysis, we propose that P. putida sigma 28 recognizes a TCAAG-t-N-12-GCCGATA consensus sequence located between -34 and -8 and that this sequence is preferentially associated with an AT-rich upstream region. (diva-portal.org)
  • Mesoscale mutational processes, the MGH Cancer Center team reasoned, merit close attention because they can target unique stretches of DNA that occur infrequently in the genome. (genengnews.com)
  • They underwent whole genome sequencing of leukemic cells collected at the diagnosis and relapse as well as normal DNA. (newswise.com)
  • We extracted cfDNA from 500 μL of plasma, which is sufficient for target mutation analysis using dPCR. (springer.com)
  • In this study we describe the cloning of the canine SLC7A9 cDNA and present a thorough mutation analysis of the coding SLC3A1 and SLC7A9 regions in cystinuric dogs of different breeds. (diva-portal.org)
  • Human thymine DNA glycosylase (TDG) was discovered as an enzyme that can initiate base excision repair at sites of 5-methylcytosine- or cytosine deamination in DNA by its ability to release thymine or uracil from G.T and G.U mismatches. (uzh.ch)
  • HhaI DNA methyltransferase belongs to the C5-cytosine methyltransferase family, which is characterized by the presence of a set of highly conserved amino acids and motifs present in an invariant order. (unthsc.edu)
  • Current evidence suggests that, in human cells, TDG and SMUG1 are the major enzymes responsible for the repair of the U:G mispairs caused by spontaneous cytosine deamination, whereas uracil arising in DNA through dU misincorporation is mainly dealt with by UNG. (wikipedia.org)
  • This entry represents various uracil-DNA glycosylases and related DNA glycosylases (EC), such as uracil-DNA glycosylase, thermophilic uracil-DNA glycosylase, G:T/U mismatch-specific DNA glycosylase (Mug), and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1). (wikipedia.org)
  • In addition, advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. (osti.gov)
  • The structure of human UNG in complex with DNA revealed that, like other glycosylases, it flips the target nucleotide out of the double helix and into the active site pocket. (wikipedia.org)
  • Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. (mdpi.com)
  • Comprehensive genomic analysis suggests that thymic carcinomas are molecularly distinct from thymomas. (aacrjournals.org)
  • In summary, parallel analyses of tumor biopsies and serial ctDNA monitoring show that lesion-specific radiographic responses to subsequent targeted therapies can be driven by distinct resistance mechanisms arising within separate tumor lesions in the same patient. (aacrjournals.org)
  • The p53 binding pattern of carcinogenic polycyclic aromatic hydrocarbons (PAHs) found in CS coincides with the p53 mutational pattern found in lung cancer, and PAHs have thus been considered to be major culprits for lung cancer. (pnas.org)
  • DNA methyltransferase 3a and 3b (Dnmt3a andDnmt3b) are two enzymes that establish this epigenetic modification during early cell development. (purdue.edu)
  • DNA can be nicked by physical shearing, over-drying or enzymes. (wikipedia.org)
  • DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. (wikipedia.org)
  • Thermostable uracil-DNA glycosylase from Thermotoga maritima a member of a novel class of DNA repair enzymes. (ebi.ac.uk)
  • More distantly related uracil-DNA glycosylases are also found in poxviruses [ PMID: 8389453 ]. (ebi.ac.uk)
  • Dressman D, Yan H, Traverso G et al (2003) Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. (springer.com)
  • Genetic analysis of the proband's available family members showed that his father, elder brother and son had also TOF. (medsci.org)
  • In order to ligate these fragments together, the ligase progresses through three steps: Addition of an adenosine monophosphate (AMP) group to the enzyme, referred to as adenylylation, Adenosine monophosphate transfer to the DNA and Nick sealing, or phosphodiester bond formation. (wikipedia.org)