Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.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).DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)Base Pairing: Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.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.Base Composition: The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.MutS DNA Mismatch-Binding Protein: A methyl-directed mismatch DNA REPAIR protein that has weak ATPASE activity. MutS was originally described in ESCHERICHIA COLI.MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.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.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.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 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.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.ThyminePlasmids: 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.GuanineTranscription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.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.Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.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)Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.Nucleic Acid Denaturation: Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Skull Base: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).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.Schiff Bases: Condensation products of aromatic amines and aldehydes forming azomethines substituted on the N atom, containing the general formula R-N:CHR. (From Grant & Hackh's Chemical Dictionary, 5th ed)DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.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)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.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)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.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)Speech Acoustics: The acoustic aspects of speech in terms of frequency, intensity, and time.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans.Tungsten: Tungsten. A metallic element with the atomic symbol W, atomic number 74, and atomic weight 183.85. It is used in many manufacturing applications, including increasing the hardness, toughness, and tensile strength of steel; manufacture of filaments for incandescent light bulbs; and in contact points for automotive and electrical apparatus.Play and Playthings: Spontaneous or voluntary recreational activities pursued for enjoyment and accessories or equipment used in the activities; includes games, toys, etc.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.

Repair of large insertion/deletion heterologies in human nuclear extracts is directed by a 5' single-strand break and is independent of the mismatch repair system. (1/1695)

The repair of 12-, 27-, 62-, and 216-nucleotide unpaired insertion/deletion heterologies has been demonstrated in nuclear extracts of human cells. When present in covalently closed circular heteroduplexes or heteroduplexes containing a single-strand break 3' to the heterology, such structures are subject to a low level repair reaction that occurs with little strand bias. However, the presence of a single-strand break 5' to the insertion/deletion heterology greatly increases the efficiency of rectification and directs repair to the incised DNA strand. Because nick direction of repair is independent of the strand in which a particular heterology is placed, the observed strand bias is not due to asymmetry imposed on the heteroduplex by the extrahelical DNA segment. Strand-specific repair by this system requires ATP and the four dNTPs and is inhibited by aphidicolin. Repair is independent of the mismatch repair proteins MSH2, MSH6, MLH1, and PMS2 and occurs by a mechanism that is distinct from that of the conventional mismatch repair system. Large heterology repair in nuclear extracts of human cells is also independent of the XPF gene product, and extracts of Chinese hamster ovary cells deficient in the ERCC1 and ERCC4 gene products also support the reaction.  (+info)

Mismatch repair and differential sensitivity of mouse and human cells to methylating agents. (2/1695)

The long-patch mismatch repair pathway contributes to the cytotoxic effect of methylating agents and loss of this pathway confers tolerance to DNA methylation damage. Two methylation-tolerant mouse cell lines were identified and were shown to be defective in the MSH2 protein by in vitro mismatch repair assay. A normal copy of the human MSH2 gene, introduced by transfer of human chromosome 2, reversed the methylation tolerance. These mismatch repair defective mouse cells together with a fibroblast cell line derived from an MSH2-/- mouse, were all as resistant to N-methyl-N-nitrosourea as repair-defective human cells. Although long-patch mismatch repair-defective human cells were 50- to 100-fold more resistant to methylating agents than repair-proficient cells, loss of the same pathway from mouse cells conferred only a 3-fold increase. This discrepancy was accounted for by the intrinsic N-methyl-N-nitrosourea resistance of normal or transformed mouse cells compared with human cells. The >20-fold differential resistance between mouse and human cells could not be explained by the levels of either DNA methylation damage or the repair enzyme O6-methylguanine-DNA methyltransferase. The resistance of mouse cells to N-methyl-N-nitrosourea was selective and no cross-resistance to unrelated DNA damaging agents was observed. Pathways of apoptosis were apparently intact and functional after exposure to either N-methyl-N-nitrosourea or ultraviolet light. Extracts of mouse cells were found to perform 2-fold less long-patch mismatch repair. The reduced level of mismatch repair may contribute to their lack of sensitivity to DNA methylation damage.  (+info)

MSH3 deficiency is not sufficient for a mutator phenotype in Chinese hamster ovary cells. (3/1695)

In the yeast Saccharomyces cerevisiae, the mutS homolog protein products MSH3 and MSH6, each in cooperation with MSH2, play well-defined and specific roles in the repair of DNA mismatches and nucleotide loops. The discrete functions of the human homologs hMSH3 and hMSH6 are less clear and current evidence suggests that the substrate specificity of these proteins may be less strict. To determine the role of MSH3 in mammalian mismatch repair, we employed MSH3-deficient Chinese hamster ovary (CHO) cell lines. No significant changes in mutation rate were detected in the MSH3-deficient strain and there were no differences in sensitivity to DNA-damaging agents. Further analysis of hprt mutants did not show a MSH3-dependent shift in the mutant spectrum. Interestingly, thorough examination of four dinucleotide microsatellite regions revealed instability at only one locus in one of the MSH3-deficient cell lines. These data support the idea of a high degree of redundancy in the function of the MutS homologs MSH3 and MSH6, at least with respect to the control of microsatellite instability.  (+info)

Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis. (4/1695)

Members of the mammalian mismatch repair protein family of MutS and MutL homologs have been implicated in postreplicative mismatch correction and chromosome interactions during meiotic recombination. Here we demonstrate that mice carrying a disruption in MutS homolog Msh5 show a meiotic defect, leading to male and female sterility. Histological and cytological examination of prophase I stages in both sexes revealed an extended zygotene stage, characterized by impaired and aberrant chromosome synapsis, that was followed by apoptotic cell death. Thus, murine Msh5 promotes synapsis of homologous chromosomes in meiotic prophase I.  (+info)

Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene. (5/1695)

Heterozygosity for germ-line mutations in the DNA mismatch repair gene MSH2 predisposes humans to cancer. Here we use a highly sensitive reporter to describe a spontaneous mutator phenotype in diploid yeast cells containing a deletion of only one MSH2 allele. We also identify five MSH2 missense mutations that have dominant mutator effects in heterozygous cells when expressed at normal levels from the natural MSH2 promoter. For example, a 230-fold mutator effect is observed in an MSH2/msh2 diploid strain in which Gly693, which is invariant in MutS homologs and involved in ATP hydrolysis, is changed to alanine. DNA binding data suggest that mismatch repair is suppressed by binding of a mutant Msh2-Msh6 heterodimer to a mismatch with subsequent inability to dissociate from the mismatch in the presence of ATP. A dominant mutator effect also is observed in yeast when Gly693 is changed to serine. An early onset colorectal tumor is heterozygous for the analogous Gly --> Ser mutation in hMSH2, and a second hMSH2 mutation was not found, suggesting that this missense mutation may predispose to cancer via a dominant mutator effect. The mutator effects of the deletion mutant and the Gly --> Ala missense mutant in yeast MSH2 are enhanced by heterozygosity for a missense mutation in DNA polymerase delta that reduces its proofreading activity but is not a mutator in the heterozygous state. The synergistic effects of heterozygosity for mutations in two different genes that act in series to correct replication errors may be relevant to cancer predisposition.  (+info)

Hypermutation in Ig V genes from mice deficient in the MLH1 mismatch repair protein. (6/1695)

During somatic hypermutation of Ig V genes, mismatched nucleotide substitutions become candidates for removal by the DNA mismatch repair pathway. Previous studies have shown that V genes from mice deficient for the MSH2 and PMS2 mismatch repair proteins have frequencies of mutation that are comparable with those from wild-type (wt) mice; however, the pattern of mutation is altered. Because the absence of MSH2 and PMS2 produced different mutational spectra, we examined the role of another protein involved in mismatch repair, MLH1, on the frequency and pattern of hypermutation. MLH1-deficient mice were immunized with oxazolone Ag, and splenic B cells were analyzed for mutations in their V kappa Ox1 light chain genes. Although the frequency of mutation in MLH1-deficient mice was twofold lower than in wt mice, the pattern of mutation in Mlh1-/- clones was similar to wt clones. These findings suggest that the MLH1 protein has no direct effect on the mutational spectrum.  (+info)

Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking. (7/1695)

The levels of proteins required for methyl-directed mismatch repair appear to decline in stationary-phase and nutritionally-deprived cells of Escherichia coli. It has been hypothesized that error-correction by the system also declines, and this decline is responsible for adaptive or stationary-phase mutations. However, evidence in support of this hypothesis is lacking. The mismatch repair system is no less effective in correcting errors during prolonged selection than it is during growth. Furthermore, mismatch repair proteins supplied in excess reduce both growth-dependent and adaptive mutation.  (+info)

MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. (8/1695)

The DNA mismatch repair (MMR) is a specialized system, highly conserved throughout evolution, involved in the maintenance of genomic integrity. To identify novel human genes that may function in MMR, we employed the yeast interaction trap. Using the MMR protein MLH1 as bait, we cloned MED1. The MED1 protein forms a complex with MLH1, binds to methyl-CpG-containing DNA, has homology to bacterial DNA repair glycosylases/lyases, and displays endonuclease activity. Transfection of a MED1 mutant lacking the methyl-CpG-binding domain (MBD) is associated with microsatellite instability (MSI). These findings suggest that MED1 is a novel human DNA repair protein that may be involved in MMR and, as such, may be a candidate eukaryotic homologue of the bacterial MMR endonuclease, MutH. In addition, these results suggest that cytosine methylation may play a role in human DNA repair.  (+info)

Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA
Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of ...
Involved in DNA mismatch repair (MMR), correcting insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of a MutL heterodimer with MLH1, which probably forms a ternary complex with the MutSbeta heterodimer that initially recognizes the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a role in the repair of heteroduplex sites present in meiotic recombination intermediates and is involved in maintaining the genetic stability of simple sequence repeats by correction of frameshift intermediates.
A simple genetic system has been developed to test the effect of over-expression of wild-type or mutated human MutL homologue 1 (hMLH1) proteins on methyl-directed mismatch repair (MMR) in Escherichia coli. The system relies on detection of Lac+ revertants using MMR-proficient or MMR-deficient E. coli strains carrying a lac +1 frameshift mutation expressing hMLH1 proteins. We report that expression of wild-type hMLH1 protein causes an approx. 19-fold increase in mutation rates. The mutator phenotype was due to the ability of hMLH1 protein to interact with bacterial MutL and MutS proteins, thereby interfering with the formation of complexes between MMR proteins and mismatched DNA. Conversely, expression of proteins encoded by alleles deriving from hereditary-non-polyposis-colon-cancer (HNPCC) families decreases mutation rates, depending on the specific amino acid substitutions. These effects parallel the MutL-and MutS-binding and ATP-binding/hydrolysis activities of the mutated proteins.. ...
SUBUNIT: Heterodimer of MLH1 and PMS1, called MutLalpha, which is the major MMR MutL activity correcting base-base mismatches as well as IDLs. The heterodimer binds double strand DNA independently of a mismatch with positive cooperativity and has more than one DNA binding site. Forms a ternary complex with either the MSH2-MSH6 (MutSalpha) or the MSH2-MSH3 heterodimer (MutSbeta), which recognize and bind to mismatch DNA. Ternary complex formation is promoted by ATP binding. Heterodimer of MLH1 and MLH3, called MutLbeta, which is involved in correction of a specific subset of IDLs when associated with MutSbeta. Heterodimer of MLH1 and MLH2 ...
A single-molecule detection setup based on total internal reflection fluorescence (TIRF) microscopy has been used to investigate association and dissociation kinetics of unlabeled 30mer DNA strands. Single-molecule sensitivity was accomplished by letting unlabeled DNA target strands mediate the binding of DNA-modified and fluorescently labeled liposomes to a DNA-modified surface. The liposomes, acting as signal enhancer elements, enabled the number of binding events as well as the residence time for high affinity binders (K-d | 1 nM, k(off) | 0.01 s(-1)) to be collected under equilibrium conditions at low pM concentrations. The mismatch discrimination obtained from the residence time data was shown to be concentration and temperature independent in intervals of 1-100 pM and 23-46 degrees C, respectively. This suggests the method as a robust means for detection of point mutations at low target concentrations in, for example, single nucleotide polymorphism (SNP) analysis.
First, the effects of intervening mismatches on DNA structure, dynamics and DNA charge transport reactivity is examined. The pi?stacked DNA base pairs mediate charge transport chemistry over long molecular distances in a reaction that is exquisitely sensitive to DNA sequence dependent conformation and dynamics. To examine the long-range charge transport as a function of intervening base mismatches, a series of DNA oligonucleotides were synthesized that incorporate a ruthenium intercalator, [Ru(phen)(bpy?)(dppz)]2+ (phen = 1,10 phenanthroline; bpy = 4-butyric acid-4-methylbipyridine; dppz = dipyrido[3,2-a:2,3-c]phenazine) linked covalently to the 5 terminus of one strand and containing two 5-GG-3 sites in the complementary strand. Single base mismatches were introduced between the two guanine doublet steps, and the efficiency of transport through the mismatches was determined through measurements of the ratio of oxidative damage at the guanine doublets distal versus proximal to the ...
In the present study, we have extended our prior analysis of 71 suspected Lynch syndrome cases as defined by a diversity of clinical criteria for MMR defects using methods that had not been previously applied to these cases. This extensive analysis has yielded several key results. First, among the 28 clearly MMR-defective cases as evidenced by their MSI-H signature, it was possible to link 27 of the cases (96%) to a defect in a known MMR gene, and in most of these cases, it was possible to identify the underlying mutation at the DNA level. This is arguably the highest or among the highest frequencies reported ( 4, 5, 21). Second, consistent with previous experience, the vast majority of mutations detected (97%) were in the MSH2 or MLH1 genes with only one mutation in PMS2 and no mutations in MSH6 detected ( 4- 6). Third, we detected mutations in cases where tumor samples were not available at the same frequency as in cases where tumor samples were available. Fourth, our ability to detect ...
pep:known chromosome:VEGA66:9:111228255:111271791:-1 gene:OTTMUSG00000031784 transcript:OTTMUST00000078764 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Mlh1 description:mutL homolog 1 (E coli ...
Mutations in DNA have far ranging consequences, from driving evolution to causing disease. DNA mismatch repair is a highly conserved process that maintains the fidelity of genomes by decreasing the mutation rate 100- to 1000-fold (Kunkel and Erie 2005). Mismatch repair proteins detect helical distortions or mismatches derived from exposure to mutagens (Stojic et al. 2004) during inexact replication of the genome (Hsieh and Yamane 2008) and upon recombination of nonidentical DNA molecules (Surtees et al. 2004). If the damaged or mismatched DNA is not repaired, and a new round of replication is initiated, the mutation becomes stably incorporated into the genome.. Lynch syndrome is a prevalent hereditary cancer syndrome caused by defects in DNA mismatch repair (Lynch et al. 2009). Individuals with Lynch syndrome are typically heterozygous for either MSH2 or MLH1, core components of DNA mismatch repair (Silva et al. 2009). As part of the disease process, the sole wild-type copy of the mismatch ...
The DNA mismatch repair (MMR) system is necessary for the maintenance of genomic stability. The MMR system promotes genomic fidelity by repairing base-base mismatches, insertion-deletion loops (IDLs) and heterologies generated during DNA replication and recombination. Failure to accomplish these functions may lead to cancer and are associated with tumor prone phenotypes.
We have engineered a mutant of HIV Reverse Transcriptase that can be fluorescently labeled by covalent attachment of the environmentally sensitive fluorophore 7-diethylamino-3-((((2-maleimidyl)ethyl)amino)carbonyl)coumarin (MDCC). The result is a polymerase that is kinetically indistinguishable from the wild-type enzyme, but provides a signal to monitor changes in enzyme structure that result from conformational changes induced by substrate binding. Using this system, we have expanded the kinetic model governing nucleotide binding to include an enzymatic isomerization following initial nucleotide binding. In doing so, we define the role of induced-fit in nucleotide specificity and mismatch discrimination. Additionally, we have characterized the kinetics governing the specificity and discrimination of several widely administered Nucleotide Reverse Transcriptase Inhibitors (NRTIs) used to combat HIV infection including 3TC (Lamivudine), FTC (Emtricitabine), and AZT (Zidovudine) for the wild-type ...
These locked nucleic acid (LNA) DNA and RNA oligonucleotides have increased Tm that can be modulated to provide greater sensitivity, SNP detection, and mismatch discrimination.
DNA mismatch repair (MMR) corrects replication errors in newly synthesized DNA. It also has an antirecombination action on heteroduplexes that contain similar but not identical sequences. This review focuses on the genetics and development of MMR and not on the latest biochemical mechanisms. The main focus is on MMR in Escherichia coli, but examples from Streptococcuspneumoniae and Bacillussubtilis have also been included. In most organisms, only MutS (detects mismatches) and MutL (an endonuclease) and a single exonucleaseare present. How this system discriminates between newlysynthesized and parental DNA strands is not clear. In E. coli and its relatives, however, Dam methylation is an integral part of MMR and is the basis for strand discrimination. A dedicated site-specific endonuclease, MutH, is present, andMutL has no endonuclease activity; four exonucleases can participate in MMR. Although it might seem that the accumulated wealth of genetic and biochemical data has given us a detailed picture of
DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preventing mutations from becoming permanent in dividing cells. MMR also suppresses homologous recombination and was recently shown to play a role in DNA damage signaling. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including HNPCC, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems. The Escherichia coli MMR pathway has been extensively studied and is well characterized. In E. coli, the mismatch-activated MutS-MutL-ATP complex licenses MutH to incise the nearest unmethylated GATC sequence. UvrD and an exonuclease generate a gap. This gap is filled by pol III and DNA ligase. The GATC sites are then methylated by Dam. Several human MMR proteins have been identified based on their homology to ...
DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preventing mutations from becoming permanent in dividing cells. MMR also suppresses homologous recombination and was recently shown to play a role in DNA damage signaling. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including HNPCC, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems. The Escherichia coli MMR pathway has been extensively studied and is well characterized. In E. coli, the mismatch-activated MutS-MutL-ATP complex licenses MutH to incise the nearest unmethylated GATC sequence. UvrD and an exonuclease generate a gap. This gap is filled by pol III and DNA ligase. The GATC sites are then methylated by Dam. Several human MMR proteins have been identified based on their homology to ...
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Mutations that prevent cells from spell-checking their DNA may make cancer cells vulnerable to immunotherapies, a new study suggests.. A type of immune therapy known as PD-1 blockade controlled cancer in 77 percent of patients with defects in DNA mismatch repair - the system cells use to spell-check and fix errors in DNA (SN Online: 10/7/15). The therapy was effective against 12 different.... ...
Difference in change in enthalpy, ΔΔHend − ΔΔHmid (dark) and change in entropy, TΔΔSend − TΔΔSmid (light), for moving a tandem mismatch from the mid
Looking for online definition of DNA mismatch repair in the Medical Dictionary? DNA mismatch repair explanation free. What is DNA mismatch repair? Meaning of DNA mismatch repair medical term. What does DNA mismatch repair mean?
Background Malignant melanoma (MM) is the most aggressive skin cancer. Most MMs are sporadic, and in this setting an association with mismatch repair (MMR) gene mutations, typical of hereditary nonpolyposis colorectal cancer (HNPCC) tumours, has been proposed.. Objectives To characterize clinically and/or by molecular biology the patients with MM belonging to a cohort of 60 kindreds with HNPCC.. Methods Patients with HNPCC with a diagnosis of MM were studied by immunohistochemistry (IHC) on tumour tissue using antibodies to MLH1, MSH2, p16, β-catenin and E-cadherin, and by direct sequencing of MMR genes on germline DNA, and BRAF and NRAS on somatic DNA extracted from MM.. Results Nine cutaneous MMs were detected in the tumour spectrum of eight families with HNPCC. The median age at diagnosis was 46 years. In one HNPCC family the diagnosis of MM was made in two first-degree relatives fitting the clinical definition of familial melanoma. IHC and sequencing analysis showed an MSH2 mutation in one ...
Medical research for Hereditary nonpolyposis colon cancer including cure research, prevention research, diagnostic research, and basic research.
The MutS homologue 6 protein (MSH6) is a member of the MutS homolog family required in the DNA mismatch repair system (1). MSH6 forms a MutS alpha dimer with MSH2, binding to DNA mismatches to initiate DNA repair (2). MutS alpha bends the DNA helix and recognizes single base mismatches and dinucleotide insertion-deletion loops in the DNA (2). Heterozygous mutations in the MSH6 gene are a cause of hereditary nonpolyposis colorectal cancer (HNPCC), forming a specific mispair binding complex with MSH3 (3, 4). The frequency of MSH6 mutation is higher in HNPCC than in atypical HNPCC (5). The MSH2/MSH6 dimer may also play a role in DNA homologous recombination repair (2 ...
Mutations in human and/or mouse homologs are associated with this disease. Synonyms: COCA 1; Hereditary Defective Mismatch Repair syndrome; hereditary non-polyposis colon cancer type 1; hereditary nonpolyposis colorectal cancer; hereditary nonpolyposis colorectal neoplasm; HNPCC - hereditary nonpolyposis colon cancer
Expression of DNA mismatch repair proteins hMSH2 and hMLH1 and the cyclin G1 inhibitor, p21(waf1/cip1) in pediatric tumors: correlation with response to therapy
Repair rates of mismatched nucleotides located at an activating hotspot of mutation, H-ras codon 12, have been analyzed in vivo in mammalian cells. Repair rates at codon 12 are significantly improved in cells synchronized to the G1 stage of the mammalian cell cycle as compared with non-synchronous cells, demonstrating that mismatch repair mechanisms are active in G1. Repair rates in non-synchronous cells for the same mismatches at a nearby non-hotspot of mutation, H-ras codon 10, are also significantly improved over repair rates at codon 12 in non-synchronous cells, demonstrating that DNA mismatch repair rates can differ depending on the sequence context. These results suggest that inefficiencies in mismatch repair are responsible, at least in part, for the well documented hotspot of mutation at codon 12. Further experiments involving gel-shift analysis demonstrate a mismatch-specific binding factor for which the degree of binding correlates with in vivo repair rates for each mismatch tested at ...
The yeast Saccharomyces cerevisiae encodes a set of genes that show strong amino acid sequence similarity to MutS and MutL, proteins required for mismatch repair in Escherichia coli. We examined the role of MSH2 and PMS1, yeast homologs of mutS and mutL, respectively, in the repair of base pair mismatches formed during meiotic recombination. By using specifically marked HIS4 and ARG4 alleles, we showed that msh2 mutants displayed a severe defect in the repair of all base pair mismatches as well as 1-, 2- and 4-bp insertion/deletion mispairs. The msh2 and pms1 phenotypes were indistinguishable, suggesting that the wild-type gene products act in the same repair pathway. A comparison of gene conversion events in wild-type and msh2 mutants indicated that mismatch repair plays an important role in genetic recombination. (1) Tetrad analysis at five different loci revealed that, in msh2 mutants, the majority of aberrant segregants displayed a sectored phenotype, consistent with a failure to repair ...
Some families with mutations in HNPCC-related genes may be tested even though they may not have all of the above characteristics. Genetic testing for Lynch syndrome should only be done after you and your doctor feel sure that it is the best thing for you and your family. It should be done by an expert counselor who can help you understand the results and what they may mean to you and your family.. The majority of Lynch syndrome cases are caused by mutations in one of several mismatch-repair genes. These mismatch-repair genes help correct "spelling errors" in DNA that happen during the cell division process. When these genes are altered, or mutated, then the "spelling errors" in the DNA cannot be repaired.. These errors in the DNA can lead to uncontrolled cell growth, which causes cancer. In Lynch syndrome, the germline mutation may be inherited from either the mother or the father and is present in all cells of the body. Whether a person who is born with a germline mutation will develop cancer, ...
Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old,
If you agree to take part in this study, you will have a single sample (8-10 teaspoons) of blood collected, depending upon current health status. The blood will be drawn at MD Anderson. If you cannot come to the clinic, a blood drawing kit will be sent to the your home, which will include instructions and a postage-paid return express mail envelope. Phlebotomy charges connected to this study will be paid by the study. The blood sample will be sent to a research laboratory at MD Anderson for analyses. If you are unwilling or unable to give a blood sample, you can give a saliva sample instead. In this case, a kit will be mailed to you with instructions for obtaining the saliva sample. A prepaid envelope will be included for its return. Participants who previously participated in Protocol PA11-0567 and provided a blood sample do not need to provide another blood sample. The previously stored blood sample collected by Protocol PA11-0567 may be used.. You will be asked to answer a series of ...
Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterized by inactivation of the DNA mismatch repair system. These cancers are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency, and have distinct pathologies. Regulatory sequences controlling all aspects of mRNA processing, especially including message stability, are found in the 3UTR sequence of most genes. The relevant sequences are typically A/U-rich elements or U repeats. Microarray analysis of 14 RER+ (deficient) and 16 RER- (proficient) colorectal cancer cell lines confirms a striking difference in expression profiles. Analysis of the incidence of mononucleotide repeat sequences in the 3UTRs, 5UTRs, and coding sequences of those genes most differentially expressed in RER+ versus RER- cell lines has shown that much of this differential expression can be explained by the occurrence of a massive enrichment of genes with 3UTR T
GLI1 and GLI2 are upregulated in a variety of human cancers and thought to participate in the development and progression of PDAC (7). Indeed, GLI1 was shown to be indispensable for KRAS-dependent pancreatic epithelial transformation in a genetically modified mouse model (32) and essential for the survival and maintenance of the transformed phenotype of human PDAC cell lines (33). Moreover, GLI1 is known to upregulate a variety of genes crucial for many properties of cancer cells, such as CYR61 (9), MUC5AC (10), and MMP9 (11) for invasion and metastasis; ABCG2 for chemoresistance (12); SNAI1 for EMT (13); BCL2 for antiapoptosis (34); and BMI1 (15, 18) and NANOG (16) for stemness. These GLI1 target genes, together with many other targets found by comprehensive screens (20-22), highlight a pivotal role of GLI1 in cancer biology, but it was still unknown whether GLI1 might be linked to the regulation of caretaker genes, which should be important in the development and progression of cancer. In the ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. MSH6 provides substrate-binding and substrate-specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. Acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis by the MutS alpha complex is crucial for MMR. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and ...
OShea JJ, Gadina M, Schreiber RD. Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 2002;109 Suppl:S121-S131. 48. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci 2004;117(Pt 8):1281-1283. 49. Hebenstreit D, Horejs-Hoeck J, Duschl A. JAK/STATdependent gene regulation by cytokines. Drug News Perspect 2005;18:243-249. 50. Lutz M, Knaus P. Integration of the TGF-beta pathway into the cellular signalling network. Cell Signal 2002;14:977- 988. 51. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 1999;9:89-96. 231. Harfe BD, Jinks-Robertson S. Mismatch repair proteins and mitotic genome stability. Mutat Res 2000;451:151- 167. 232. Harfe BD, Jinks-Robertson S. DNA mismatch repair and genetic instability. Annu Rev Genet 2000;34:359-399. 233. Aquilina G, Bignami M. Mismatch repair in correction of replication errors and processing of DNA damage. J Cell Physiol 2001;187:145-154. 234. Hsieh P. Molecular mechanisms of DNA mismatch repair. Mutat Res ...
2017 - English Colorectal carcinoma (CRC) is one of the most prevalent malignancies in the Czech Republic. In general, there are two molecular pathways leading to CRC: one is characterized by chromosomal instability, the other by the deficiency in DNA mismatch repair (MMR) genes. MutL homologue 1 (MLH1) gene, a member of the MMR gene-family, represents a key component of the MMR system, responsible for recognition of nucleotide mismatches occurring during DNA replication, and for the recruitment of repair proteins to correct the replication errors. According to literature, somatic mutations in MMR genes, and MLH1 in particular, hallmark sporadic, MMR deficient, CRC cases. We aimed at analyzing somatic events in MLH1 gene and the determination of microsatellite instability (MSI) status in 99 DNA samples from 96 patients with sporadic CRC. Mutations were screened by high resolution melting (HRM) curve analysis. Positive cases in each run were subsequently verified by automated sequencing. Mainly ...
TY - JOUR. T1 - T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers. AU - Asaka, Shiho. AU - Yen, Ting Tai. AU - Wang, Tian-Li. AU - Shih, Ie Ming. AU - Gaillard, Stephanie. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is fundamental to developing future immune-based interventions. This study aimed to determine the immune cell populations associated with mismatch repair-deficient endometrial cancers, especially focusing on targetable regulatory pathways of the immune response. A total of 76 endometrial cancer hysterectomy specimens were evaluated for tumor-infiltrating immune cells by immunohistochemistry. Immune specific markers were used to evaluate each specimen for the number ...
We describe the effect of nearest-neighbor sequence context on mismatch-dependent activation of hMSH2-hMSH6. Examination of the intrinsic sequences that occur around symmetric mismatched nucleotides suggests little if any effect of non-nearest-neighbor base pairs on hMSH2-hMSH6 mismatch recognition and ATPase activation (20), although longer-range effects have been reported (22). Although a sequence context effect is not novel in MMR (21), the underlying mechanism is unknown. Our studies have suggested that when a significant nearest-neighbor sequence context effect is manifest, 2 × 3′-purines enhanced, and 2 × 3′-pyrimidines reduced hMSH2-hMSH6 ATPase activation (kcat). A similar trend is observed for mismatch binding (KD), whereas an inverse effect was observed for the Tm of unbound mismatched oligonucleotides. Importantly, the KD and Tm do not accurately account for hMSH2-hMSH6 ATPase activation. Interestingly, the effect of sequence context on KD appears associated with alteration of ...
Microsatellite instability (MSI) testing analyzes colon, endometrial, and other tumor tissue samples. It can be used to screen tumors for mismatch repair deficiency (MMRd), and to find individuals who may be at-risk for Lynch syndrome. The results of MSI testing can guide the next steps for your patient with regards to treatment recommendations, as well as further testing for Lynch syndrome. ...
Eric Alani is a Professor in the Department of Molecular Biology and Genetics. Dr. Alani is a member of both the Graduate Field of Genetics, Genomics and Development and the Graduate Field of Biochemistry, Molecular and Cell Biology. The Alani lab studies roles for DNA mismatch repair proteins in maintaining genome stability.
There is provided a resonator sensor useful for detecting polymorphisms and mutations in DNA. The resonator sensor has a capture molecule immobilised on its surface, the capture molecule being either a probe DNA containing a reference sequence, or a mismatch binding molecule, and being capable of forming a probe DNA/target DNA/mismatch binding molecule complex on the surface of the resonator. A method for detecting mutations in a target DNA, including single nucleotide polymorphisms, is also provided ...
Histogram of the mismatch frequencies for the different base pairs within cTAR. Mismatch base pairs are preferentially flanking the two well-conserved G10 and G
Complete information for PMS2 gene (Protein Coding), PMS1 Homolog 2, Mismatch Repair System Component, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
In a small group of women with mismatch repair (MMR) deficiency endometrial uterine cancer, survival was increased by pembrolizumab.
The program mmfind evaluates an alignment in multiple FASTA format for mismatches. Quality scores are considered if a file with scores is supplied. Several options for filtering are available. The detected mismatches are tested for 3 meaningful qualities. mmfind is a commandline tool written in Python. It is tested with Python 2.6, 2.7 and 3.1. ...
The program mmfind evaluates an alignment in multiple FASTA format for mismatches. Quality scores are considered if a file with scores is supplied. Several options for filtering are available. The detected mismatches are tested for 3 meaningful qualities. mmfind is a commandline tool written in Python. It is tested with Python 2.6, 2.7 and 3.1. ...
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TY - JOUR. T1 - Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer. AU - Bronner, C. Eric. AU - Baker, Sean M.. AU - Morrison, Paul T.. AU - Warren, Gwynedd. AU - Smith, Leslie G.. AU - Lescoe, Mary Kay. AU - Kane, Michael. AU - Earabino, Christine. AU - Lipford, James. AU - Lindblom, Annika. AU - Tannergård, Pia. AU - Bollag, Roni J.. AU - Godwin, Alan R.. AU - Ward, David C.. AU - Nordenskjøld, Magnus. AU - Fishel, Richard. AU - Kolodner, Richard. AU - Liskay, R. Michael. PY - 1994/1/1. Y1 - 1994/1/1. N2 - THE human DNA mismatch repair gene homologue, hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC)1,2. On the basis of linkage data, a second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3). Here we report that a human gene encoding a protein, hMLHl (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human chromosome 3p21.3-23. We propose ...
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer. It is inherited as an autosomal dominant syndrome (see the image below), as a result of defective mismatch repair (MMR) proteins.
DNA mismatch repair (MMR) is a highly conserved system that repairs DNA adducts acquired during replication, as well as some forms of exogenous/endogenous DNA damage. Additionally, MMR proteins bind to DNA adducts that are not removed by MMR and influence damage-response mechanisms other than repair. Hereditary non-polyposis colorectal cancer, as well as mouse models for MMR deficiency, illustrate that MMR proteins are required for maintenance of genetic stability and tumor suppression. In both humans and mice, the phenotype associated with Msh6-associated tumorigenesis is distinct from that of Msh2. In this study, we hypothesized that Msh6−/−;p53+/− mice would display earlier tumor onset than their Msh6−/− or p53+/− counterparts, indicating that concomitant loss of these two tumor suppressors contributes to tumorigenesis via mechanisms that are only partially interrelated. We generated a Msh6−/−;p53+/− mouse model which succumbed to malignant disease at an accelerated rate and ...
Yoon, S. N., Ku, J.-L., Shin, Y.-K., Kim, K.-H., Choi, J.-S., Jang, E.-J., Park, H.-C., Kim, D.-W., Kim, M. A., Kim, W. H., Lee, T. S., Kim, J. W., Park, N.-H., Song, Y.-S., Kang, S.-B., Lee, H.-P., Jeong, S.-Y. and Park, J.-G. (2008), Hereditary nonpolyposis colorectal cancer in endometrial cancer patients. Int. J. Cancer, 122: 1077-1081. doi: 10.1002/ijc.22986 ...
HNPCC (hereditary non-polyposis colon cancer) is an autosomal-dominant disorder characterized by early-onset CRC (colorectal cancer). HNPCC is most often associated with mutations in the MMR (mismatch repair) genes hMLH1, hMSH2, hMSH6 or hPMS2. The mutator phenotype of a defective MMR system is MSI (microsatellite instability), which also occurs in approx. 15-25% of sporadic CRC cases, where it is associated with the hypermethylation of the promoter region of hMLH1. Dietary factors, including excessive alcohol consumption, ingestion of red meat and low folate intake, may increase the risk of MSI high tumour development. In contrast, aspirin may suppress MSI in MMR-deficient CRC cell lines. Butyrate, a short-chain-fatty-acid end product of carbohydrate fermentation in the colon, shares a number of anti-neoplastic properties with aspirin, including inhibiting proliferation and inducing apoptosis of CRC cells. Recent in vitro studies suggest that physiological concentrations of butyrate (0.5-2 mM) ...
This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013 ...
Lynch Syndrome (OMIM 120435), also called Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an inherited cancer syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. MMR genes are responsible for repairing small sequence errors, or mismatches, during DNA replication. Mutations in a single mismatch repair gene can cause widespread genomic instability characterized by the expansion or contraction of short tandem repeat sequences (microsatellites) (reviewed by Grady & Carethers in Gastroenterology 135:1079-1099, 2008). This phenomenon of microsatellite instability (MSI) leads to somatic mutations in oncogenes and/or tumor suppressor genes, including TGFβIIR and NF1 among others (Wang et al. Hum Genet 112:117-123, 2003). As a result, Lynch Syndrome is marked by early onset and high lifetime risk of cancer, particularly in the right colon but also in the endometrium, ovary, stomach, bile duct, kidney, bladder, ureter, and brain (Jang & Chung, Gut and Liver 4:151-160, 2010). ...
Results of Sensitivity Analysis:. The model was most sensitive to the estimated survival gain from screening siblings and children, to the prevalence of HNPCC mutations among patients with newly diagnosed cancer, and to the discount rate. In probabilistic analysis, the 90% CI for the cost-effectiveness of screening patients with cancer plus their relatives was $4874 to $21 576 per life-year gained. ...
Sigma-Aldrich offers abstracts and full-text articles by [Ruth I Tennen, Joanna E Haye, Hashanthi D Wijayatilake, Tim Arlow, Danielle Ponzio, Alison E Gammie].
Polyamides are a class of DNA minor groove binders that were developed from the natural product Distamycin A. PA25 (20-ring PA) showed better activity (3-fold) in the elimination of HPV16 episomes than PA1 (14-ring PA). Binding studies of PA1 and PA25 were performed in the long control region of HPV16 (7348-122 bp). PA1 showed similar binding affinity to perfect match and single mismatch binding sites. PA1 bound to double, triple, and quadruple mismatch sites with lower affinity. PA25 bound with similar binding affinity to perfect through triple mismatch binding sites. PA25 bound quadruple mismatch sites and nonspecifically. Therefore, it was concluded that PA25 is better at accommodating mismatches in its binding sites. The serine hydrolase family has a catalytic triad that consists of Serine, Histidine, and Glutamic/Aspartic Acid. Acetylcholinesterase (AChE) belongs to the serine hydrolase family. AChE hydrolyzes acetylcholine to stop signal transmission between neurons and thus is a drug target for
Mammalian MutL homologues function in DNA mismatch repair (MMR) after replication errors and in meiotic recombination. Both functions are initiated by a heterodimer of MutS homologues specific to either MMR (MSH2-MSH3 or MSH2-MSH6) or crossing over (MSH4-MSH5). Mutations of three of the four MutL homologues (Mlh1, Mlh3, and Pms2) result in meiotic defects. We show herein that two distinct complexes involving MLH3 are formed during murine meiosis. The first is a stable association between MLH3 and MLH1 and is involved in promoting crossing over in conjunction with MSH4-MSH5. The second complex involves MLH3 together with MSH2-MSH3 and localizes to repetitive sequences at centromeres and the Y chromosome. This complex is up-regulated in Pms2−/− males, but not females, providing an explanation for the sexual dimorphism seen in Pms2−/− mice. The association of MLH3 with repetitive DNA sequences is coincident with MSH2-MSH3 and is decreased in Msh2−/− and Msh3−/− mice, suggesting a ...
Predicting patient outcome for colorectal carcinoma (CRC) with lymph node but not distant metastases remains challenging. Various prognostic markers have been identified including microsatellite instability (MSI) and possibly expression of the MHC Class II protein, HLA-DR. About 15% of sporadic CRC exhibits MSI associated with methylation of the DNA mismatch repair gene hMLH1 promoter. In addition, a significant proportion of unselected CRC demonstrates expression of HLA-DR. We sought to examine the relationship between HLA-DR expression, MSI status and prognosis in sporadic Australian Clinicopathological (ACP) Stage C CRC. Two hundred seventy consecutive patients with sporadic ACP Stage C CRC were treated at Concord Repatriation General Hospital between 1986 and 1992. None of these patients received adjuvant chemotherapy and all were followed for a minimum of 5 years or until death. DNA was extracted from paraffin sections and MSI status determined by PCR. HLA-DR expression was determined ...
Our studies are aimed at revealing the molecular-level mechanisms used by the cellular protein system that locates base mismatch errors and some types of damage in DNA and then signals for their repair. Defects of this protein system are involved in multiple types of cancer including colon (especially hereditary non-polyposis colorectal cancer), ovarian, prostate, bladder and sporadic leukemia. Mutations in these cellular proteins that can occur during the course of tumor growth often result in development of tumor resistance to chemotherapeutic treatments.. We engineer DNA substrates and recombinant versions of the mismatch repair proteins to allow attachment of fluorescent dyes at specific locations. We then use the FRET method to record realtime information about how the conformations of these molecules change as they encouter mismatches and recruit partner proteins that carry out repair. Our project is a collaboration with Dorothy Eries group at UNC-Chapel Hill. ...
Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Mutation carriers are at substantially increased risk of developing cancers of the colorectum and endometrium, among others. Given recent recommendations for universal, cost-effective screening of all patients with newly diagnosed colorectal cancer using MMR protein immunohistochemistry, we evaluated MMR protein expression in a series of endometrial cancers in the general population. A total of 605 consecutive cases of primary endometrial cancer at a single institution (1997 to 2013) were evaluated regardless of age, family history, or histologic features. Evaluation methods consisted of immunohistochemistry for the MMR proteins MLH1, MSH2, MSH6, and PMS2, followed by DNA methylation analysis for cases with MLH1/PMS2 deficiency. Germline mutation testing was performed on a subset of cases. Forty MMR-deficient, nonmethylated endometrial cancers were identified: 3 ...
This chapter concentrates on the repair mechanism in Escherichia coli, but the lessons learned in this organism should also apply to analogous systems in other organisms. Although there are several distinct DNA mismatch repair systems, in this chapter the term is used to denote the MutSLH system. DNA polymerase III, the replicative enzyme, catalyzes resynthesis of nucleotides and ligation followed by Dam methylation to complete the process. An alternative to the futile cycling model based on double-strand DNA breaks (DSBs) recombinational repair is described in the chapter to explain how mismatch repair sensitizes E. coli dam mutants (and human cells) to methylating agents and cisplatin. In dam mutants there is constant repair of DSBs, and the recombinational capacity of the cell is probably near its maximum. This conclusion is based on the higher basal level of transcription of certain SOS genes in dam cells, suggesting that one or more of the RecA or RuvA or RuvB proteins is limiting. The hypothesis
The SCOP classification for the DNA repair protein MutS, domain II superfamily including the families contained in it. Additional information provided includes InterPro annotation (if available), Functional annotation, and SUPERFAMILY links to genome assignments, alignments, domain combinations, taxonomic visualisation and hidden Markov model information.
Foram avaliados 528 isolados clínicos de Pseudomonas aeruginosa de 131 pacientes fibrocísticos atendidos em um centro de referência em fibrose cística (FC) durante o período de 2005 a 2008. 135 isolados clínicos (25,6%) apresentaram subpopulação hipermutante (isolados com altas taxas de mutações) utilizando teste modificado de suscetibilidade aos antimicrobianos. Destes, 9 isolados (6,7%) de 7 pacientes foram classificados como hipermutantes (HPM) segundo estimativa da freqüência de mutação. Após seqüenciamento do gene mutS e análise de mutações relacionadas à inativação do sistema de reparo de erros no pareamento do DNA (Mismatch Repair System - MRS), foi possível observar este tipo de mutação em 5 isolados HPM de 4 pacientes. Avaliamos a formação de biofilme em 45 isolados NHPM, 9 HPM e suas respectivas subpopulações por duas metodologias. Segundo o primeiro método, 24 (53,3%) e 3 (21,4%) isolados NHPM e HPM, respectivamente, foram classificados como ...
Q: What do you do as a lab technician?. I work in the Molecular Genetics lab here at Ambry. I run tests for HNPCC (Hereditary nonpolyposis colorectal cancer). I pull patient DNA in the morning and set up PCR reactions for multiple exons of the gene that causes the disease. After the reactions are done I run the products on a gel to verify amplification. I love having a perfect gel: clear band after clear band with a clean negative and a passing positive looks so beautiful!. Q: What was your most significant experience studying biology at Biola?. During our last semester, my lab partner and I conducted an independent research project on sea squirts for Developmental Biology. The time put into this project was easily one of the most interesting, challenging, and faith building moments of my time there. While my entire experience at Biola certainly contributed to building a more cohesive appreciation and understanding of the experiment, it was the opportunities to learn first hand with your own ...
Gang Liu 00:55, 14 May 2009 (EST)meiosis flowchartMeiosis flowchart --Linda Taylor 09:49, 14 May 2009 (EST)Hi all! I will not be at the lab today as I have a throat infection. --Lisa Mak 11:15, 14 May 2009 (EST)Take care Linda and get well soon! --Jae Lee 03:32, 16 May 2009 (EST) hey guys, Ive done some simple restructuring and I think it looks a little better than previously. and i would just like to let you know that im still working on regulation of meiosis, and it will be completed soon~ --Jae Lee 13:51, 18 May 2009 (EST) Hey, Im going to change my protein for the individual project to Spo11 protein, its a key protein involved in initiation of meiotic recombination. I tried to continue with my DNA mismatch repair protein... but it seemed really broad and complex. Anyways, I hope you guys are progressing well with your individual assignment-! --Linda Taylor 15:06, 26 May 2009 (EST)Hi guys, have just done a bit of editing. Jae, thanks for the Regulation posts and Lisa, thanks for Meiosis II ...
811533DNAM.yongonense 1atggccatct tcaccagcat ccttgacccc ggagtggatg accgcggcag tagctcgcca 60ccctcaccag acttcctcgc cgaccttcat ctcgaccaga tcttcgccgc ggtgacggct 120gggtatggcg acagtgagat cgcgagtact ttctgtgcac ccctccatga cctgcgggct 180gtgcagtacc gccagcaagt gttccgtgac ctcgaggacg agcacacacg gtcatcgata 240caaaacttcg tcgacggcat ccgtgccatg cgcggtcgac ttaccgtggc gaggaacgcg 300tggcaccgcc tgcaacgaca gggttggcta atcgctgcga tcgagattta ttgccgcaca 360atagaactgc taggcaataa tgtcgccgac atgagaatgc gttcgccggg cttgcgcaac 420ttcgctgagc acgttacggg ctacatcaat ggcgaggctt tcaagacgct ggccgccgag 480acccaaacga tgcgagacca tctgcgcaga gtgcgataca tggtgcacat tgagggcctt 540caagttcatg tccaaaagtt caacgaacaa agtgattaca gtacggccat cgctgaaacg 600tttgaacgtt tcgcgacgga ggtcagcaag gactaccgtg tcgcgcttcc ggaattcaac 660gatatgaacc atatcgagga gcagattctc gaatgcgtcg ctagacttca tccggaagcc 720tttaggcttc tcgatagctt ctgccacaat cacgaacact ttatagaacc gattgttgcg 780agatttgagc acgagatcca cttctatctc tcatatctga tgttcatcgg ccgtttcagg 840acgctgggac tcgcgttttg ...
Duppatla, Viswanadham and Bodda, Chiranjeevi and Urbanke, Claus and Friedhoff, Peter and Rao, Desirazu N (2009) The C-terminal domain is sufficient for endonuclease activity of Neisseria gonorrhoeae MutL. In: Biochemical Journal, 423 (Part 2). pp. 265-277. Joseph, Nimesh and Duppatla, Viswanadham and Rao, Desirazu N (2005) Functional characterization of the DNA mismatch binding protein MutS from Haemophilus influenzae. In: Biochemical and Biophysical Research Communications, 334 (3). pp. 891-900. ...
An exemplary signal processing system determines vector mismatch between a plurality of signal paths. Advantageously, the system can determine mismatch across a range of frequencies. A signal generator of the system can provide a periodic calibration signal having a plurality of frequency components. The system frequency can translate the calibration signal to provide a first set of observed samples. The first sample set can be compared to a second set of samples, which can be modeled by a function of parameters including an estimated vector mismatch and a plurality of basis functions. A value of vector mismatch can then be determined (at least to an estimate) that minimizes the difference between the first sample set and the second sample set. Methods and other systems with different advantageous configurations are also described.
Im doing the analysis by bouncing the file back and forth a couple of times between Word and Excel, using Word to first insert tabs between the output lines, and then Excel to delete the columns (formerly lines) I dont want (including the actual sequences) and to sort the results by both the match score and the locations of the ends of the matches. Then I use Word to insert tabs between each position of each alignment, and Excel to count the numbers of mismatches at each position and to graph the results ...
PMS for those who have experienced it, can make you feel like a wild woman out of control, but the good news is that you dont have to suffer anymore.
The Bethesda criteria are an alternative to the Amsterdam criteria for the clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). Diagnosis of HNPCC is made if any of the following criteria are fulfilled: Amsterdam criteria ...
DNA repeat expansion underlies dozens of progressive neurodegenerative disorders. While the mechanisms driving repeat expansion are not fully understood, increasing evidence suggests a central role for DNA mismatch repair. The mismatch repair recognition complex MutSβ (MSH2-MSH3) that binds mismatched bases and/or insertion/deletion loops has previously been implicated in GAA•TTC, CAG•CTG and CGG•CCG repeat expansion, suggesting a shared mechanism. MutSβ has been studied in a number of models, but the contribution of subsequent steps mediated by the MutL endonuclease in this pathway is less clear. Here we show that MutLγ (MLH1-MLH3) is the MutL complex responsible for GAA•TTC repeat expansion. Lentiviral expression of shRNA targeting MutL nuclease components MLH1, PMS2, and MLH3 revealed that reduced expression of MLH1 or MLH3 reduced the repeat expansion rate in a human Friedreich ataxia cell model, while targeting PMS2 did not. Using splice-switching oligonucleotides we show that ...
Patients who have had colorectal cancer and who are carriers of the DNA mismatch repair gene mutations that cause Lynch syndrome "have an increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers," according to a study in the Journal of the National Cancer Institute.. Previous studies had shown that mutation carriers "are at a substantially increased risk of cancers of the colon, rectum, endometrium, stomach, ovary, ureter, renal pelvis, brain, small bowel, hepatobiliary tract, and pancreas," the authors noted. A major inherited cancer syndrome, Lynch syndrome is also known as hereditary nonpolyposis colorectal cancer (HNPCC).. The study was based on data for 764 patients from the Colon Cancer Family Registry, evenly divided between men and women, who were carriers of the mismatch repair gene mutation and previously diagnosed with colorectal cancer. Most of the carriers (52%) were recruited in Australia and New ...
HNPCC is an autosomal dominant disease that is clinically characterized by the development of colorectal cancer (CRC) at an early age (mean age 44 years old). Four genes have been known to be related to this hereditary disease. It shows an excess of synchronous and metachronous tumors as well as a preponderance of right-sided tumors (70%). Another feature has been seen among the families of the HNPCC patients is the occurrence of adenocarcinomas at other sites (particularly at the endometrial, ovary, stomach, pancreas, ureter, renal pelvis, and skin). Difficulties arise in distinguishing environmental factors and genetic predisposition for familial clustering of CRC. The discovery of HNPCC germline mutations has been momentous in that it enables a clear distinction between carriers and noncarriers for those who were previously assigned a 50% risk of germline mutation. The informed consent provided by patients is important for the process of familial study and the search for germline mutations, ...
Mismatch repair protein deficiency (MMR-D) and high microsatellite instability (MSI-H) are features of Lynch syndrome-associated colorectal carcinomas and have implications in clinical management. We evaluate the ability of a targeted next-generation sequencing panel to detect MMR-D and MSI-H based on mutational phenotype. Using a criterion of ,40 total mutations per megabase or ,5 single-base insertion or deletion mutations in repeats per megabase, sequencing achieves 92% sensitivity and 100% specificity for MMR-D by immunohistochemistry in a training cohort of 149 colorectal carcinomas and 91% sensitivity and 98% specificity for MMR-D in a validation cohort of 94 additional colorectal carcinomas. False-negative samples are attributable to tumor heterogeneity, and next-generation sequencing results are concordant with analysis of microsatellite loci by PCR. In a subset of 95 carcinomas with microsatellite analysis, sequencing achieves 100% sensitivity and 99% specificity for MSI-H in the ...
The MSH1 and MSH2 genes of Saccharomyces cerevisiae are predicted to encode proteins that are homologous to the Escherichia coli MutS and Streptococcus pneumoniae HexA proteins and their homologs. Disruption of the MSH1 gene caused a petite phenotype which was established rapidly. A functional MSH1 gene present on a single-copy centromere plasmid was incapable of rescuing the established msh1 petite phenotype. Analysis of msh1 strains demonstrated that mutagenesis and large-scale rearrangement of mitochondrial DNA had occurred. 4,6-Diamidino-2-phenylindole (DAPI) staining of msh1 yeast revealed an aberrant distribution of mtDNA. Haploid msh2 mutants displayed an increase of 85-fold in the rate of spontaneous mutation to canavanine resistance. Sporulation of homozygous msh2/msh2 diploids gave rise to a high level of lethality which was compounded during increased vegetative growth prior to sporulation. msh2 mutations also affected gene conversion of two HIS4 alleles. The his4x mutation, lying ...
Lyle Simmons. MutS is responsible for initiating the correction of DNA replication errors. To understand how MutS searches for and identifies rare base-pair mismatches, we characterized the dynamic movement of MutS and the replisome in real time using superresolution microscopy and single-molecule tracking in living cells. We report that MutS dynamics are heterogeneous in cells, with one MutS population exploring the nucleoid rapidly, while another MutS population moves to and transiently dwells at the replisome region, even in the absence of appreciable mismatch formation. Analysis of MutS motion shows that the speed of MutS is correlated with its separation distance from the replisome and that MutS motion slows when it enters the replisome region. We also show that mismatch detection increases MutS speed, supporting the model for MutS sliding clamp formation after mismatch recognition. Using variants of MutS and the replication processivity clamp to impair mismatch repair, we find that MutS ...
When DNA MMR enzyme expression in RA was compared with OA, hMSH3 and hMSH6 levels as determined by the percentage of the region containing the protein were modestly higher in RA (p,0.01). However, hMSH2 expression in RA was similar to OA (table 1, figs 1 and 2). The data on hMSH6 expression compare with the results of our recent study of synovial microsatellite instability, in which hMSH6 expression was decreased in RA compared with OA by western blot analysis.3 This apparent difference is probably due to the techniques employed. Western blot provides an accurate representation of normalised protein expression but lacks the spatial resolution of immunohistochemistry. Despite this limitation, the immunostaining can identify the primary sites of protein expression and can give insights into the percentage of the tissue that expresses the protein of interest. Therefore, these two techniques provide complementary information.. To determine which cells in the synovium express the MMR proteins, double ...
Several mutations recently have been shown to be associated with hereditary nonpolyposis colon cancer HNPCC in families displaying unusually strong predisposition to colorectal cancer. Laboratory tests to detect such gene mutations soon will be commercially available, raising the possibility for population-wide screening. The purpose of this...
The risk of metachronous colonic neoplasia after proctectomy for rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is understudied and remains incompletely defined. This study reports a 51.5% rate of high-risk adenoma or adenocarcinoma in the colon after proctectomy. Although surgical decisions need to be individualized, total proctocolectomy should be the preferred treatment for an index rectal cancer in a patient with HNPCC ...
The researchers found that single mismatched ribonucleotides in chromosomal DNA were removed by either the mismatch repair system or RNase H type 2. Mismatched ribonucleotides in the middle of at least four other ribonucleotides required RNase H type 1 for removal.. "We were excited to find that a DNA repair mechanism like mismatch repair was activated by RNA/DNA mismatches and could remove ribonucleotides embedded in chromosomal DNA," explained Storici. "In future studies, we plan to test whether other DNA repair mechanisms, such as nucleotide-excision repair and base-excision repair, can also locate and remove ribonucleotides in DNA.". Using gene correction assays driven by short nucleic acid polymers called oligonucleotides, the researchers showed that when ribonucleotides embedded in DNA were not removed, they served as templates for DNA synthesis and produced a mutation in the DNA. If both the mismatch repair system and RNase H repair mechanisms are disabled, ribonucleotide-driven gene ...
The 2 most common inherited bowel cancer syndromes are hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). Learn more about them here.
Cisplatin). In addition, radiosensitization by thymidine analogues such as IUdR is enhanced in MMR-deficient cells because of inability to remove the modified base. The MMR status of cells is therefore of importance for outcome, not for radiotherapy alone, but for combinations of radiotherapy with some chemotherapy or radiosensitizing agents. Nucleotide excision repair copes with bulky lesions, such as those caused by UV light (thymine dimers), and DNA adducts induced by cisplatin. However, as with MMR, knocking out NER genes has, in general, little effect on sensitivity to ionizing radiation, and so no detailed discussion of NER will be included here. The link between SSBs and DSBs Single-strand breaks can lead to the formation of DSBs in two main ways. First, ionizing radiation damage often occurs in clusters, such that some SSBs will also have damage to DNA bases in their near vicinity. 8). It has been shown that, if base damage occurs on the opposite strand to a radiation-induced SSB, the ...
Approximately 1.6 million single nucleotide polymorphisms (SNPs) have been identified and deposited in public databases, but more are always needed for studies of other species and identification of mutations in candidate disease genes. In the January Nature Biotechnology, Nakatani et al. outline a new method for SNP identification using capture by a mismatch-specific ligand followed by surface plasmon resonance (SPR; Nat Biotechnol 2001, 19:51-55). The ligand, a dimeric naphthyridine, intercalates into and base-pairs with a G-G mismatch, discriminating against other mismatches. Mismatch-containing DNA is trapped by the immobilized ligand, and the DNA then changes the reflective index of polarized light hitting the SPR chip. There are disadvantages: ligands for other mismatches do not yet exist, and SPR does not identify the location of the mutation within the probed DNA fragment. But SPR can be automated, and the re-usable system requires no labeling of DNA or other probes.. ...
Mammalian cells have evolved sophisticated DNA repair systems to correct mispaired or damaged bases and extra helical loops. However, we find that two DNA repair systems, the mismatch recognition system (MMR) and the base excision repair, are turned into
MSH5, 50 µg. MSH5 is a member of the mutS family of proteins that are involved in DNA mismatch repair or meiotic recombination processes.
The US Food and Drug Administration has cleared use of Merck & Co’s immunotherapy Keytruda to treat cancer patients identified as having a biomarker called microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). - News - PharmaTimes
The goal of the Alani laboratory is to understand how MMR proteins interact to prevent replication errors and to modulate genetic recombination.
I have the WORST pms. A week before my cycle and then the week of my cycle. So I am only capable of being a nice person 2 weeks of the month. My husband
Futurebiotics PMSHarmony 56 caps advanced pms complex clinically proven nutrients for nutritional pms support* BioResponse DIM ...
article{f44be10d-a333-4ee8-bd99-2b50129274c5, abstract = {,p,We have screened 17 Southern Sweden individuals/families with suspected hereditary non-polyposis colorectal cancer (HNPCC) for mutations in the DNA-mismatch repair genes hMLH1, hMSH2 and hMSH6 using denaturing gradient gel electrophoresis, protein truncation test and direct DNA sequencing. The families were selected on the basis of a family history of HNPCC-related tumors or the occurrence of metachronous colorectal cancer/endometrial cancer at young age in an individual with a weak family history of cancer. Furthermore, we required that tumor tissue from at least one individual in the family had to display microsatellite instability. We identified germ-line mutations in 9 individuals from 8 families. Five families had mutations in hMLH1, 4 of which were splice site mutations, 2 had frameshift mutations in hMSH2 and 1 patient with metachronous endometrial and rectal cancer but with a weak family history of cancer had a nonsense ...
RAS/RAF mutation and defective DNA mismatch repair in endometrial cancers. Persistent and recurrent cervical dysplasia after loop electrosurgical excision procedure
The subtype of Muir-Torre syndrome, allelic to hereditary nonpolyposis colorectal cancer is typically associated with germline mutations in the mismatch repair proteins MSH-2 and/or MLH-1. More recently, mutation in an additional mismatch repair protein MSH-6 has been documented in a patient with Muir-Torre syndrome. Given this, the aim of the present study was to ascertain the frequency of the same in unselected sebaceous gland neoplasms. Overall, we found that 59% of sebaceous neoplasms exhibited a mutation in at least one mismatch repair protein gene -- a prevalence rate similar to that reported previously by others. Of interest, we found MSH-6 to be the mismatch repair protein most commonly lost 17/41 (41%), followed by MSH-2 14/41 (34%) and MLH-18/41 (20%) and the positive predictive value of each were as follows: MLH-1 88%, MSH-6 67% and MSH-2 55%. The frequency of a MSH-6 germline mutation in our cohort indicates that it is not a rare finding. Evidence indicating microsatellite stability in three
To date, two forms of microsatellite instability (MSI) have been described in human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due to deficient DNA mismatch repair (MMR) and is defined with mono- and dinucleotide repeat microsatellites. A second variety of instability is best seen at selective tetranucleotide repeats (EMAST; elevated microsatellite alterations at select tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is common. Sporadic tumours with the largest proportion showing MSI are those found most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low frequency of MSI in bladder cancer, we sought to determine the relative levels of MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary tracts. Microsatellite analysis was performed at 10 mono- and dinucleotide and eight tetranucleotide loci, in 89 bladder and 71 UTT
The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal ...
A study of families with Lynch Syndrome has expanded the list of cancers related to the condition: carriers of a Lynch Syndrome gene mutation also appear to have an increased risk of breast cancer and pancreatic cancer. These results were published in the Journal of Clinical Oncology.. Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), results from inherited mutations in genes involved in DNA mismatch repair. These mutations greatly increase the risk of developing colorectal cancer. In individuals with Lynch Syndrome, the average age at diagnosis of colorectal cancer is about 44 years, compared with 64 years in the general population. Overall, roughly 3% to 5% of all colorectal cancers are thought to result from Lynch Syndrome. Several other types of cancer are also known to be more common in people with Lynch Syndrome, including cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis.. To further explore cancer risk ...
Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the USA, Canada and Australia and screened probands for mutations in mismatch repair genes and MUTYH. We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the probands age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of and hazard ratio for unidentified major gene mutations, and the variance of the residual polygenic component. Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1= 1 in 1946, MSH2= 1 in 2841, MSH6= 1 in 758, PMS2= 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30-50% after allowing for unidentified major genes and decreased from 3.3 ...
Purpose: Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Patients and Methods: Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Results: Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified
DNA repair mechanisms are biased towards repairing a mismatch to the CG base pair. This will lead allele frequencies to change ... Meiotic recombination between homologous chromosomes that are heterozygous at a particular locus can produce a DNA mismatch. ...
Thus, it changes a C:G base pair into a mutagenic U:G mismatch. In a still further cause of DNA damage, HCV core protein binds ... AID creates mutations in DNA by deamination (a DNA damage) of the cytosine base, which converts cytosine into uracil. ... including the base of the tongue and tonsils). Each year in the United States, about 39,800 new cases of cancer are found in ...
Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs. Nucleotide excision repair (NER) is a particularly ... Base excision repair (BER) Mismatch repair (MMR) Fuss JO, Cooper PK (June 2006). "DNA repair: dynamic defenders against cancer ... Karahalil B, Bohr V, Wilson D (October 2012). "Impact of DNA polymorphisms in key DNA base excision repair proteins on cancer ... Zhang Y, Rohde LH, Wu H (June 2009). "Involvement of nucleotide excision and mismatch repair mechanisms in double strand break ...
In early part of his academic career, Brown studied base-pair mismatch and DNA repair. Later he worked on the mutagenic effect ... "Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair". Nature (320): 552-555. 10 April ... "High-resolution structure of a DNA helix containing mismatched base pairs". Nature. 315: 694-606. 13 June 1985. Bibcode: ... "Four base recognition by triplex-forming oligonucleotides at physiological pH". Nucleic Acids Research. 33 (9): 3025-3032. 12 ...
Su, SS; Modrich, P (July 1986). "Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs". Proceedings of the ... He works primarily on strand-directed mismatch repair. His lab demonstrated how DNA mismatch repair serves as a copyeditor to ... He is known for his research on DNA mismatch repair. Modrich received the Nobel Prize in Chemistry 2015, jointly with Aziz ... They later searched for proteins associated with mismatch repair in humans. Dr. Modrich is also a fellow of the American ...
Mismatches in DNA base pairing can potentially result in dysfunctional proteins and could lead to cancer. Many DNA polymerase ... When an incorrect base pair is recognized, DNA polymerase moves backwards by one base pair of DNA. The 3'-5' exonuclease ... Hydrogen bonds play a key role in base pair binding and interaction. The loss of an interaction, which occurs at a mismatch, is ... Hunter, Brown; Anand, Kennard (1986). "Structure of an adenine-cytosine base pair in DNA and its implications for mismatch ...
G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a ... This allows the generation of mutations at AT base pairs. The level of AID activity in B cells is tightly controlled by ... This heterodimer is able to recognize mostly single-base distortions in the DNA backbone, consistent with U:G DNA mismatches. ... The U:G mismatch may also be recognized by the DNA mismatch repair (MMR) machinery, to be specific by the MutSα(alpha) complex ...
... exonuclease activity that acts preferentially on mismatched base pairs". Nucleic Acids Res. 34 (9): 2508-15. doi:10.1093/nar/ ... Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER). Its main ... Because APE1 performs an essential function in DNA base-excision repair pathway, it has become a target for researchers looking ... Mark R. Kelley; Melissa L. Fishel (2007). "The DNA base excision repair protein Ape1/Ref-1 as a Therapeutic and chemopreventive ...
... uses an oligonucleotide that is complementary to a bacterial plasmid with a single base pair mismatch or a series of mismatches ... This primer will have a base pair mismatch at the site where the replacement is desired. The primer must also be long enough ... A single base pair replacement, could change a codon, and thus replace an amino acid in a protein. This is useful for studying ... PCR paired with Western blotting and ELISA help define the relationship between cancer cells and IL-6. Enzyme-linked ...
Complex for High-affinity DNA Base-pair Mismatch Recognition". Proceedings of the National Academy of Sciences. 100 (7): 3737- ... of metallo-intercalators is to combat cancerous tumor cells within the body by targeting specific mismatched DNA base pairs; ... This ability to bind to specific DNA base pairs allows for potential therapeutic applications of metallo-intercalators. In the ... metallo-intercalator and DNA can substantially decrease the proliferation of cells containing DNA with mismatched base pairs. ...
G pair into an T:A pair, effectively changing a base and introducing a mutation. This misincorporated base will not be ... This results in a T:G mismatch. Repair mechanisms then correct it back to the original C:G pair; alternatively, they may ... If there is a mis-match, it is recorded and the percentage of DNA for which the mis-match is present is noted. This gives the ... The three base pairs flanking each side of this site also influence DNA-Dam binding. Dam plays several key roles in bacterial ...
The predicted double stranded region is 30 base pairs in length. The adenosine residue is mismatched in genomically encoded ... The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS) The pre-mRNA of this ... The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with ... Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become ...
... relies upon the sensitivity of DNA ligase for base-pairing mismatches. The target molecule to be ... Instead, the mismatch sensitivity of a DNA ligase enzyme is used to determine the underlying sequence of the target DNA ... This sequences every Nth base, where N is the length of the probe left behind after cleavage. To sequence the skipped positions ... Although commonly represented as joining two pairs of ends at once, as in the ligation of restriction enzyme fragments, ligase ...
"Hydrolysis by restriction endonucleases at their DNA recognition sequences substituted with mismatched base pairs". Nucleic ... Bilcock DT, Daniels LE, Bath AJ, Halford SE (December 1999). "Reactions of type II restriction endonucleases with 8-base pair ... T basepairs". FEBS Lett. 143 (2): 296-300. doi:10.1016/0014-5793(82)80120-8. PMID 6288466. Marks P, McGeehan J, Wilson G, ...
The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS). The editing site was ... The predicted double-stranded RNA structure is interrupted by three bulges and a mismatch at the editing site. The double- ... The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site, with ... stranded region is 22 base pairs in length. As with editing of the KCNA1 gene product, the editing region and the editing ...
This modification results in mismatched base-pairing between inosine and uridine, leading to the destabilization and unwinding ... The conversion from A to I in the RNA disrupt the normal A:U pairing which makes the RNA unstable. Inosine is structurally ... Luo GX, Chao M, Hsieh SY, Sureau C, Nishikura K, Taylor J (1990). "A specific base transition occurs on replicating hepatitis ...
however most are nonspecific, instead recognizing structural abnormalities produced in the DNA backbone by base pair mismatches ... would be predicted to occur every 256 base pairs on average (where 4^4=256), but any given six-base sequence would be expected ... They found that the HindII enzyme always cuts directly in the center of this sequence (between the 3rd and 4th base pairs) Most ... DNA mismatch repair in any given organism is effected by a suite of mismatch-specific endonucleases. In prokaryotes, this role ...
DNA polymerase reverses its direction by one base pair of DNA and excises the mismatched base. Following base excision, the ... When an incorrect base pair is recognized, ... polymerase can re-insert the correct base and replication can ...
This is due to base-pair mismatching generated as a result of destabilised heteroduplex annealing between wild-type and variant ... as expected from the higher thermostability of the GC base pair In a field more relevant to clinical diagnostics, HRM has been ... HRM is more cost effective and reduces the need to design multiple pairs of primers and the need to purchase expensive probes. ... 2003, showed that fluorescent labelling of one primer (in the pair) has been shown to be favourable over using an intercalating ...
... double-stranded DNA exonuclease that may act in a pathway that corrects mismatched base pairs; yeast DHS1, yeast DIN7. Sequence ...
... or non Watson-Crick base pairs in the a DNA duplex. Some sources of mismatched base pairs include replication errors and ... DNA mismatch repair (MMR) is an important DNA repair system that helps maintain genome plasticity by correcting mismatches, ... Nicks are also thought to play a role in the DNA mismatch repair mechanisms that fix errors on both the leading and lagging ... MMR in most bacteria and eukaryotes is directed to the erroneous strand of the mismatched duplex through recognition of strand ...
The base pairing in pseudoknots is not well nested; that is, base pairs occur that "overlap" one another in sequence position. ... The only other possible pairings are GT and AC; these pairings are mismatches because the pattern of hydrogen donors and ... In the canonical Watson-Crick base pairing, adenine (A) forms a base pair with thymine (T) and guanine (G) forms one with ... such as the wobble base pair and Hoogsteen base pair, also occur-particularly in RNA-giving rise to complex and functional ...
... but similarities in sequence and other factors can result in mismatched alignments. Most DNA is composed of base pair sequences ... Mismatch repair (MMR) proteins, for instance, are a well-known regulatory family of proteins, responsible for regulating ... One class of MMR in particular, MutSβ, is known to initiate the correction of insertion-deletion mismatches of up to 16 ... A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous ...
... occurs during meiosis when homologous recombination between heterozygotic sites results in a mismatch in base pairing. This ... For example, when a T:G mismatch occurs, it would be more or less likely to be corrected to a C:G pair than a T:A pair. This ... Conversion of one allele to the other is often due to base mismatch repair during homologous recombination: if one of the four ... When mismatches occur in heteroduplex DNA, the sequence of one strand will be repaired to bind the other strand with perfect ...
... this is an example where a Watson-Crick basepair mismatch is stabilized by the formation of the metal-base pair. Another ... The asymmetric metal base pairing system is orthogonal to the Watson-Crick base pairs. Another example of an artificial ... 2012). "Highly specific unnatural base pair systems as a third base pair for PCR amplification". Nucleic Acids Research. 40 (6 ... base pair. One of the most common base analogs is 5-bromouracil (5BU), the abnormal base found in the mutagenic nucleotide ...
In addition, a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the ... A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. ... The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or ... Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease. ...
It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase ... Altered dynamics of DNA bases adjacent to a mismatch: a cue for mismatch recognition by MutS.. J. Mol. Biol. 374 39-53 2007 ... The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch.. Nature 407 711-7 2000 ... which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch [PMID: 17951114]. MutS exists as a ...
Dynamics of mismatched base pairs in DNA.. Guest CR1, Hochstrasser RA, Sowers LC, Millar DP. ... The structural dynamics of mismatched base pairs in duplex DNA have been studied by time-resolved fluorescence anisotropy decay ... These differences are correlated with the strength of base-pairing interactions in the various AP.X mismatches. The ... in the strength of base-pairing interactions at a specific site in DNA by observing their effect on the dynamics of base motion ...
... base pair mismatch include Methods to Increase the Sensitivity of High Resolution Melting Single Nucleotide Polymorphism ... Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of ... Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (Nucleic acid heteroduplexes). Methods to ... cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. ...
... base pairs represent the most common type of DNA damage, as they are permanently formed in living cells due to erroneous ... In vivo, they are readily recognised and repaired by the proteins of the DNA mismatch repair system, which ... Mismatched (non-Watson-Crick) base pairs represent the most common type of DNA damage, as they are permanently formed in living ... Finding needles in a basestack: recognition of mismatched base pairs in DNA by small molecules A. Granzhan, N. Kotera and M. ...
identifying single base mismatch probes, said single base mismatch probes comprising at least two of A, C, T, U, and G ... Hybridization and sequencing of nucleic acids using base pair mismatches Abstract. Devices and techniques for hybridization of ... As shown herein, the moderate stablility of probe/target complexes with single base pair mismatches generates families of ... The method as recited in claim 14 wherein said affinity of single base mismatch probes are plotted as affinity versus mismatch ...
A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch ... Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae.. P Detloff, ... Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. ... Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. ...
Fluo- rescence resonance energy transfer (FRET) was used as an indicator for unwinding of dsDNA due to base pair mismatch at ... A simple method using water-soluble conjugated polymers and a DNA intercalator has been proposed for single base pair mismatch ... Tian, N., Tang, Y., Xu, Q.-H., Wang, S. (2007-03-16). Single base pair mismatch detection using cationic conjugated polymers ... Single base pair mismatch detection using cationic conjugated polymers through fluorescence resonance energy transfer. ...
A rule of seven in Watson-Crick base-pairing of mismatched sequences (I. I. Cisse, H. Kim, T. Ha), In Nat. Struct. Mol. Biol., ... A rule of seven in Watson-Crick base-pairing of mismatched sequences ... rick base-pairing of mismatched sequences}, Journal=Nat. Struct. Mol. Biol., Year=2012, Volume=19, Number=6, Pages= ...
The present invention provides methods for specifically detecting DNA mismatches between heteroduplex strands produced between ... Such variants include mismatches in base pairing caused by annealing of wildtype and mutant DNA strands to form heteroduplexes ... Methods and kits for fractionating a population of DNA molecules based on the presence or absence of a base-pair mismatch ... followed by the heteroduplex mismatches expected upon hybridization of a wildtype strand with each of the potential base pair ...
The effect of single base pair mismatch. Nucleic Acids Res. 6:3543-3557.PubMedPubMedCentralCrossRefGoogle Scholar ... Arrangement of base sequences in deoxyribonucleic acid. Bacteriol. Rev. 31:215-229.PubMedPubMedCentralGoogle Scholar ... Base composition-independent hybridization in tetramethylammonium chloride: A method for oligonucleotide screening of highly ... an alternative to standard sequencing as a means of direct analysis of chromosomal DNA to determine the spectrum of single-base ...
Adaptation, Biological • Algorithms • Amino Acid Sequence • Approximation algorithms • Base Pair Mismatch • Bayes Theorem • ...
1986) Structures of mismatched base pairs in DNA and their recognition by the Escherichia coli mismatch repair system. EMBO J 5 ... 1986) Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs. Proc Natl Acad Sci USA 83:5057-5061. ... The gray box shows ATPase activation by a homoduplex DNA containing an A/T or G/C base pair at the mismatch site (± standard ... 2006) Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34:564-574 ...
pyrimidine-specific mismatch base pair DNA N-glycosylase activity IDA Inferred from Direct Assay. more info ... G/5-fluorouracil mismatch glycosylase with biphasic kinetics. G/T mismatch glycosylase. G/U mismatch glycosylase. methyl-CpG ... Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, ... Involvement of MBD4 inactivation in mismatch repair-deficient tumorigenesis. Tricarico R, et al. Oncotarget, 2015 Dec 15. PMID ...
Mismatches around switching stems *Mismatches in hairpin loop in switching stem. *Patterns for closing basepairs in the ... Stretches of pyrimidines (C and U) pairing with stretches of purine. (G and A). 4-way Stem Switch. I did try out make a 4 stem ... Now also the pairing probability plot goes missing when I change engine, and the melt plot remains the same for all engines. ... so maybe I just picked the pair of nubmers that looks like it could match in the not-so-small group that doesnt work? not sure ...
... terms of base pair mismatch? For instance, does a figure of 12% , divergence between the same stretch of DNA in two bacterial ... mismatches would occur in 3 out , of 4 cases). , , Is this the method used to generate similarity estimates? Any assistance , ...
... to the T*G mismatch-containing oligonucleotides than to the sequences with other mismatched or with Watson-Crick base pairs. ... f-ImImIm associates more slowly with DNAs containing T*G mismatches in place of one or two C*G base pairs and, more importantly ... was recently found using NMR methods to recognize T*G mismatched base pairs. In order to characterize in detail the T*G ... A*G or G*G mismatched base pairs) hairpin oligonucleotides were determined by surface plasmon resonance and circular dichroism ...
1991 Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol. ... the heteroduplex will contain mismatches. Although most base-base mismatches (with the exception of C/C) or mismatches with one ... 1991 Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae. Genetics 129: 669-673. ... Mismatches near the initiating lesion were repaired exclusively by conversion-type repair, whereas mismatches located far away ...
Base Pair Mismatch / genetics* * Base Sequence * Cystic Fibrosis / microbiology * DNA Helicases / genetics* ... The Mismatch Repair System (mutS, mutL and uvrD Genes) in Pseudomonas Aeruginosa: Molecular Characterization of Naturally ... Here, we report the cloning and sequencing of two additional P. aeruginosa mismatch repair genes and the characterization, by ... showing defective mismatch repair activity. Interestingly, cells carrying this mutant allele exhibited a fully active UvrABC- ...
... each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the ... Base Pair Mismatch * DNA Polymerase II / genetics * DNA Polymerase II / metabolism * DNA Polymerase III / genetics ... Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than ... each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the ...
1993) Cytosine deamination in mismatched base pairs. Biochemistry 32:6523-6530.. OpenUrlCrossRefPubMed ... 1995) Sequence specificity for removal of uracil from U.A pairs and U.G mismatches by uracil-DNA glycosylase from Escherichia ... 1996) Mapping nucleosome position at single base-pair resolution by using site-directed hydroxyl radicals. Proc Natl Acad Sci ... we used synthesized 150 base oligonucleotides containing the 15 base canonical glucocorticoid receptor response element (GRE) ...
... the process by which mismatches introduced during DNA replication are corrected. We demonstrate that the C terminus of Bacillus ... MutS homologs function in several cellular pathways including mismatch repair (MMR), ... Base Pair Mismatch* * DNA Mismatch Repair* * Green Fluorescent Proteins / metabolism * Models, Molecular ... MutS homologs function in several cellular pathways including mismatch repair (MMR), the process by which mismatches introduced ...
II prevents erroneous transcription in vitro with different strategies that depend on the type of DNARNA base mismatch. Certain ... Other mismatches allow for RNA extension but are inefficiently formed and effi … ... mismatches are efficiently formed but impair RNA extension. ... TU mismatch impairs RNA extension by forming a wobble base pair ... Certain mismatches are efficiently formed but impair RNA extension. Other mismatches allow for RNA extension but are ...
3.5.1 BASE PAIR MISMATCH 3.5.2 POOR BINDING 3.5.3 HYBRIDIZATION 3.5.4 VARIABLE SIGNAL STRENGTHS 3.5.5 INTERPRETATION OF ... 4.4.4.2 Functional genomics & genomic mis-match scanning 4.4.4.3 Reverse genetics 4.4.4.4 Diagnosis & genetic mapping 4.4.5 ... China and India being the most populous countries would provide the largest base for clinical trials and drug discovery; and ... and genomic mismatch scanning, gene mapping, diagnosis), SNP analysis, screening & monitoring of patient data during clinical ...
... maximum basepair distance: 100; minimum number of basepairs: 7; number of mismatch 1 suboptimal (Busch et al., 2008; Smith et ... maximal base pair span 150, temperature 40°C, energy parameter set rna_turner2004.par, minimal pair probability 5.0E-4, minimal ... Wurtzel, O., Sapra, R., Chen, F., Zhu, Y., Simmons, B. A., and Sorek, R. (2010). A single-base resolution map of an archaeal ... The following parameters were used: word size 28, expected threshold 10, match score 1, mismatch score -2, linear gap costs, ...
DNA mismatch repair (MMR) corrects mismatched base pairs mainly caused by DNA replication errors. The fundamental mechanisms ... recognizes base-base mismatches and nicks the - or -side of the mismatched base on the discontinuous strand. The resulting DNA ... speculated the possibility that a mismatched base is flipped out upon mismatch recognition by MutS [54]. Base flipping is one ... After recognition of a mismatched base by , incises the discontinuous strand of the heteroduplex in a mismatch-. -, PCNA-, RFC ...

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