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).
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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).
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)
Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.
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.
The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
A methyl-directed mismatch DNA REPAIR protein that has weak ATPASE activity. MutS was originally described in ESCHERICHIA COLI.
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.
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.
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.
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.
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.
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.
Thymine is a pyrimidine nucleobase, one of the four nucleobases in the nucleic acid of DNA (the other three being adenine, guanine, and cytosine), where it forms a base pair with adenine.
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.
Guanine is a purine nucleobase, one of the four nucleobases in the nucleic acid of DNA and RNA, involved in forming hydrogen bonds between complementary base pairs in double-stranded DNA molecules.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
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.
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)
A pyrimidine base that is a fundamental unit of nucleic acids.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
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)
The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.
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).
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.
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)
Deoxyribonucleic acid that makes up the genetic material of bacteria.
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)
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.
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)

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)

A base pair mismatch is a type of mutation that occurs during the replication or repair of DNA, where two incompatible nucleotides pair up instead of the usual complementary bases (adenine-thymine or cytosine-guanine). This can result in the substitution of one base pair for another and may lead to changes in the genetic code, potentially causing errors in protein synthesis and possibly contributing to genetic disorders or diseases, including cancer.

A nucleic acid heteroduplex is a double-stranded structure formed by the pairing of two complementary single strands of nucleic acids (DNA or RNA) that are derived from different sources. The term "hetero" refers to the fact that the two strands are not identical and come from different parents, genes, or organisms.

Heteroduplexes can form spontaneously during processes like genetic recombination, where DNA repair mechanisms may mistakenly pair complementary regions between two different double-stranded DNA molecules. They can also be generated intentionally in laboratory settings for various purposes, such as analyzing the similarity of DNA sequences or detecting mutations.

Heteroduplexes are often used in molecular biology techniques like polymerase chain reaction (PCR) and DNA sequencing, where they can help identify mismatches, insertions, deletions, or other sequence variations between the two parental strands. These variations can provide valuable information about genetic diversity, evolutionary relationships, and disease-causing mutations.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Oligodeoxyribonucleotides (ODNs) are relatively short, synthetic single-stranded DNA molecules. They typically contain 15 to 30 nucleotides, but can range from 2 to several hundred nucleotides in length. ODNs are often used as tools in molecular biology research for various applications such as:

1. Nucleic acid detection and quantification (e.g., real-time PCR)
2. Gene regulation (antisense, RNA interference)
3. Gene editing (CRISPR-Cas systems)
4. Vaccine development
5. Diagnostic purposes

Due to their specificity and affinity towards complementary DNA or RNA sequences, ODNs can be designed to target a particular gene or sequence of interest. This makes them valuable tools in understanding gene function, regulation, and interaction with other molecules within the cell.

DNA repair is the process by which cells identify and correct damage to the DNA molecules that encode their genome. DNA can be damaged by a variety of internal and external factors, such as radiation, chemicals, and metabolic byproducts. If left unrepaired, this damage can lead to mutations, which may in turn lead to cancer and other diseases.

There are several different mechanisms for repairing DNA damage, including:

1. Base excision repair (BER): This process repairs damage to a single base in the DNA molecule. An enzyme called a glycosylase removes the damaged base, leaving a gap that is then filled in by other enzymes.
2. Nucleotide excision repair (NER): This process repairs more severe damage, such as bulky adducts or crosslinks between the two strands of the DNA molecule. An enzyme cuts out a section of the damaged DNA, and the gap is then filled in by other enzymes.
3. Mismatch repair (MMR): This process repairs errors that occur during DNA replication, such as mismatched bases or small insertions or deletions. Specialized enzymes recognize the error and remove a section of the newly synthesized strand, which is then replaced by new nucleotides.
4. Double-strand break repair (DSBR): This process repairs breaks in both strands of the DNA molecule. There are two main pathways for DSBR: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly rejoins the broken ends, while HR uses a template from a sister chromatid to repair the break.

Overall, DNA repair is a crucial process that helps maintain genome stability and prevent the development of diseases caused by genetic mutations.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

DNA mismatch repair (MMR) is a cellular process that helps to correct errors that occur during DNA replication and recombination. This mechanism plays a critical role in maintaining the stability of the genome by reducing the rate of mutations.

The MMR system recognizes and repairs base-base mismatches and small insertions or deletions (indels) that can arise due to slippage of DNA polymerase during replication. The process involves several proteins, including MutSα or MutSβ, which recognize the mismatch, and MutLα, which acts as a endonuclease to cleave the DNA near the mismatch. Excision of the mismatched region is then carried out by exonucleases, followed by resynthesis of the repaired strand using the correct template.

Defects in MMR genes have been linked to various human diseases, including hereditary nonpolyposis colorectal cancer (HNPCC) and other types of cancer. In HNPCC, mutations in MMR genes lead to an accumulation of mutations in critical genes, which can ultimately result in the development of cancer.

Base pairing is a specific type of chemical bonding that occurs between complementary base pairs in the nucleic acid molecules DNA and RNA. In DNA, these bases are adenine (A), thymine (T), guanine (G), and cytosine (C). Adenine always pairs with thymine via two hydrogen bonds, while guanine always pairs with cytosine via three hydrogen bonds. This precise base pairing is crucial for the stability of the double helix structure of DNA and for the accurate replication and transcription of genetic information. In RNA, uracil (U) takes the place of thymine and pairs with adenine.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Base composition in genetics refers to the relative proportion of the four nucleotide bases (adenine, thymine, guanine, and cytosine) in a DNA or RNA molecule. In DNA, adenine pairs with thymine, and guanine pairs with cytosine, so the base composition is often expressed in terms of the ratio of adenine + thymine (A-T) to guanine + cytosine (G-C). This ratio can vary between species and even between different regions of the same genome. The base composition can provide important clues about the function, evolution, and structure of genetic material.

Nucleic acid conformation refers to the three-dimensional structure that nucleic acids (DNA and RNA) adopt as a result of the bonding patterns between the atoms within the molecule. The primary structure of nucleic acids is determined by the sequence of nucleotides, while the conformation is influenced by factors such as the sugar-phosphate backbone, base stacking, and hydrogen bonding.

Two common conformations of DNA are the B-form and the A-form. The B-form is a right-handed helix with a diameter of about 20 Å and a pitch of 34 Å, while the A-form has a smaller diameter (about 18 Å) and a shorter pitch (about 25 Å). RNA typically adopts an A-form conformation.

The conformation of nucleic acids can have significant implications for their function, as it can affect their ability to interact with other molecules such as proteins or drugs. Understanding the conformational properties of nucleic acids is therefore an important area of research in molecular biology and medicine.

The MutS DNA mismatch-binding protein is a key component of the bacterial DNA mismatch repair system, which plays a crucial role in maintaining genomic stability by correcting errors that occur during DNA replication. This protein is responsible for recognizing and binding to mismatched base pairs or small insertion/deletion loops (known as heteroduplexes) that escape the proofreading activity of polymerase enzymes.

Once bound to a mismatch, MutS undergoes a conformational change and recruits other proteins to form a complex that initiates the repair process. The complex uses the intact strand as a template to remove the incorrect segment, followed by resynthesis of the corrected sequence. This enzyme is highly conserved across various species, including humans, where it is involved in similar DNA repair processes and has been implicated in several hereditary cancer syndromes.

MutS Homolog 2 (MSH2) Protein is a type of protein involved in the DNA repair process in cells. It is a member of the MutS family of proteins, which are responsible for identifying and correcting mistakes that occur during DNA replication. MSH2 forms a complex with another MutS homolog, MSH6, and this complex plays a crucial role in recognizing and binding to mismatched base pairs in the DNA. Once bound, the complex recruits other proteins to repair the damage and restore the integrity of the DNA. Defects in the MSH2 gene have been linked to an increased risk of certain types of cancer, including hereditary non-polyposis colorectal cancer (HNPCC) and uterine cancer.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

'Escherichia coli' (E. coli) is a type of gram-negative, facultatively anaerobic, rod-shaped bacterium that commonly inhabits the intestinal tract of humans and warm-blooded animals. It is a member of the family Enterobacteriaceae and one of the most well-studied prokaryotic model organisms in molecular biology.

While most E. coli strains are harmless and even beneficial to their hosts, some serotypes can cause various forms of gastrointestinal and extraintestinal illnesses in humans and animals. These pathogenic strains possess virulence factors that enable them to colonize and damage host tissues, leading to diseases such as diarrhea, urinary tract infections, pneumonia, and sepsis.

E. coli is a versatile organism with remarkable genetic diversity, which allows it to adapt to various environmental niches. It can be found in water, soil, food, and various man-made environments, making it an essential indicator of fecal contamination and a common cause of foodborne illnesses. The study of E. coli has contributed significantly to our understanding of fundamental biological processes, including DNA replication, gene regulation, and protein synthesis.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Thymine is a pyrimidine nucleobase that is one of the four nucleobases in the nucleic acid double helix of DNA (the other three being adenine, guanine, and cytosine). It is denoted by the letter T in DNA notation and pairs with adenine via two hydrogen bonds. Thymine is not typically found in RNA, where uracil takes its place pairing with adenine. The structure of thymine consists of a six-membered ring (pyrimidine) fused to a five-membered ring containing two nitrogen atoms and a ketone group.

A plasmid is a small, circular, double-stranded DNA molecule that is separate from the chromosomal DNA of a bacterium or other organism. Plasmids are typically not essential for the survival of the organism, but they can confer beneficial traits such as antibiotic resistance or the ability to degrade certain types of pollutants.

Plasmids are capable of replicating independently of the chromosomal DNA and can be transferred between bacteria through a process called conjugation. They often contain genes that provide resistance to antibiotics, heavy metals, and other environmental stressors. Plasmids have also been engineered for use in molecular biology as cloning vectors, allowing scientists to replicate and manipulate specific DNA sequences.

Plasmids are important tools in genetic engineering and biotechnology because they can be easily manipulated and transferred between organisms. They have been used to produce vaccines, diagnostic tests, and genetically modified organisms (GMOs) for various applications, including agriculture, medicine, and industry.

Guanine is not a medical term per se, but it is a biological molecule that plays a crucial role in the body. Guanine is one of the four nucleobases found in the nucleic acids DNA and RNA, along with adenine, cytosine, and thymine (in DNA) or uracil (in RNA). Specifically, guanine pairs with cytosine via hydrogen bonds to form a base pair.

Guanine is a purine derivative, which means it has a double-ring structure. It is formed through the synthesis of simpler molecules in the body and is an essential component of genetic material. Guanine's chemical formula is C5H5N5O.

While guanine itself is not a medical term, abnormalities or mutations in genes that contain guanine nucleotides can lead to various medical conditions, including genetic disorders and cancer.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

Hydrogen bonding is not a medical term per se, but it is a fundamental concept in chemistry and biology that is relevant to the field of medicine. Here's a general definition:

Hydrogen bonding is a type of attractive force between molecules or within a molecule, which occurs when a hydrogen atom is bonded to a highly electronegative atom (like nitrogen, oxygen, or fluorine) and is then attracted to another electronegative atom. This attraction results in the formation of a partially covalent bond known as a "hydrogen bond."

In biological systems, hydrogen bonding plays a crucial role in the structure and function of many biomolecules, such as DNA, proteins, and carbohydrates. For example, the double helix structure of DNA is stabilized by hydrogen bonds between complementary base pairs (adenine-thymine and guanine-cytosine). Similarly, the three-dimensional structure of proteins is maintained by a network of hydrogen bonds that help to determine their function.

In medical contexts, hydrogen bonding can be relevant in understanding drug-receptor interactions, where hydrogen bonds between a drug molecule and its target protein can enhance the binding affinity and specificity of the interaction, leading to more effective therapeutic outcomes.

A gene is a specific sequence of nucleotides in DNA that carries genetic information. Genes are the fundamental units of heredity and are responsible for the development and function of all living organisms. They code for proteins or RNA molecules, which carry out various functions within cells and are essential for the structure, function, and regulation of the body's tissues and organs.

Each gene has a specific location on a chromosome, and each person inherits two copies of every gene, one from each parent. Variations in the sequence of nucleotides in a gene can lead to differences in traits between individuals, including physical characteristics, susceptibility to disease, and responses to environmental factors.

Medical genetics is the study of genes and their role in health and disease. It involves understanding how genes contribute to the development and progression of various medical conditions, as well as identifying genetic risk factors and developing strategies for prevention, diagnosis, and treatment.

Oligonucleotides are short sequences of nucleotides, the building blocks of DNA and RNA. They typically contain fewer than 100 nucleotides, and can be synthesized chemically to have specific sequences. Oligonucleotides are used in a variety of applications in molecular biology, including as probes for detecting specific DNA or RNA sequences, as inhibitors of gene expression, and as components of diagnostic tests and therapies. They can also be used in the study of protein-nucleic acid interactions and in the development of new drugs.

Cytosine is one of the four nucleobases in the nucleic acid molecules DNA and RNA, along with adenine, guanine, and thymine (in DNA) or uracil (in RNA). The single-letter abbreviation for cytosine is "C."

Cytosine base pairs specifically with guanine through hydrogen bonding, forming a base pair. In DNA, the double helix consists of two complementary strands of nucleotides held together by these base pairs, such that the sequence of one strand determines the sequence of the other. This property is critical for DNA replication and transcription, processes that are essential for life.

Cytosine residues in DNA can undergo spontaneous deamination to form uracil, which can lead to mutations if not corrected by repair mechanisms. In RNA, cytosine can be methylated at the 5-carbon position to form 5-methylcytosine, a modification that plays a role in regulating gene expression and other cellular processes.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

DNA restriction enzymes, also known as restriction endonucleases, are a type of enzyme that cut double-stranded DNA at specific recognition sites. These enzymes are produced by bacteria and archaea as a defense mechanism against foreign DNA, such as that found in bacteriophages (viruses that infect bacteria).

Restriction enzymes recognize specific sequences of nucleotides (the building blocks of DNA) and cleave the phosphodiester bonds between them. The recognition sites for these enzymes are usually palindromic, meaning that the sequence reads the same in both directions when facing the opposite strands of DNA.

Restriction enzymes are widely used in molecular biology research for various applications such as genetic engineering, genome mapping, and DNA fingerprinting. They allow scientists to cut DNA at specific sites, creating precise fragments that can be manipulated and analyzed. The use of restriction enzymes has been instrumental in the development of recombinant DNA technology and the Human Genome Project.

Nucleic acid denaturation is the process of separating the two strands of a double-stranded DNA molecule, or unwinding the helical structure of an RNA molecule, by disrupting the hydrogen bonds that hold the strands together. This process is typically caused by exposure to high temperatures, changes in pH, or the presence of chemicals called denaturants.

Denaturation can also cause changes in the shape and function of nucleic acids. For example, it can disrupt the secondary and tertiary structures of RNA molecules, which can affect their ability to bind to other molecules and carry out their functions within the cell.

In molecular biology, nucleic acid denaturation is often used as a tool for studying the structure and function of nucleic acids. For example, it can be used to separate the two strands of a DNA molecule for sequencing or amplification, or to study the interactions between nucleic acids and other molecules.

It's important to note that denaturation is a reversible process, and under the right conditions, the double-stranded structure of DNA can be restored through a process called renaturation or annealing.

Restriction mapping is a technique used in molecular biology to identify the location and arrangement of specific restriction endonuclease recognition sites within a DNA molecule. Restriction endonucleases are enzymes that cut double-stranded DNA at specific sequences, producing fragments of various lengths. By digesting the DNA with different combinations of these enzymes and analyzing the resulting fragment sizes through techniques such as agarose gel electrophoresis, researchers can generate a restriction map - a visual representation of the locations and distances between recognition sites on the DNA molecule. This information is crucial for various applications, including cloning, genome analysis, and genetic engineering.

DNA repair enzymes are a group of enzymes that are responsible for identifying and correcting damage to the DNA molecule. These enzymes play a critical role in maintaining the integrity of an organism's genetic material, as they help to ensure that the information stored in DNA is accurately transmitted during cell division and reproduction.

There are several different types of DNA repair enzymes, each responsible for correcting specific types of damage. For example, base excision repair enzymes remove and replace damaged or incorrect bases, while nucleotide excision repair enzymes remove larger sections of damaged DNA and replace them with new nucleotides. Other types of DNA repair enzymes include mismatch repair enzymes, which correct errors that occur during DNA replication, and double-strand break repair enzymes, which are responsible for fixing breaks in both strands of the DNA molecule.

Defects in DNA repair enzymes have been linked to a variety of diseases, including cancer, neurological disorders, and premature aging. For example, individuals with xeroderma pigmentosum, a rare genetic disorder characterized by an increased risk of skin cancer, have mutations in genes that encode nucleotide excision repair enzymes. Similarly, defects in mismatch repair enzymes have been linked to hereditary nonpolyposis colorectal cancer, a type of colon cancer that is inherited and tends to occur at a younger age than sporadic colon cancer.

Overall, DNA repair enzymes play a critical role in maintaining the stability and integrity of an organism's genetic material, and defects in these enzymes can have serious consequences for human health.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Sequence homology in nucleic acids refers to the similarity or identity between the nucleotide sequences of two or more DNA or RNA molecules. It is often used as a measure of biological relationship between genes, organisms, or populations. High sequence homology suggests a recent common ancestry or functional constraint, while low sequence homology may indicate a more distant relationship or different functions.

Nucleic acid sequence homology can be determined by various methods such as pairwise alignment, multiple sequence alignment, and statistical analysis. The degree of homology is typically expressed as a percentage of identical or similar nucleotides in a given window of comparison.

It's important to note that the interpretation of sequence homology depends on the biological context and the evolutionary distance between the sequences compared. Therefore, functional and experimental validation is often necessary to confirm the significance of sequence homology.

Adenine is a purine nucleotide base that is a fundamental component of DNA and RNA, the genetic material of living organisms. In DNA, adenine pairs with thymine via double hydrogen bonds, while in RNA, it pairs with uracil. Adenine is essential for the structure and function of nucleic acids, as well as for energy transfer reactions in cells through its role in the formation of adenosine triphosphate (ATP), the primary energy currency of the cell.

Nucleic acid hybridization is a process in molecular biology where two single-stranded nucleic acids (DNA, RNA) with complementary sequences pair together to form a double-stranded molecule through hydrogen bonding. The strands can be from the same type of nucleic acid or different types (i.e., DNA-RNA or DNA-cDNA). This process is commonly used in various laboratory techniques, such as Southern blotting, Northern blotting, polymerase chain reaction (PCR), and microarray analysis, to detect, isolate, and analyze specific nucleic acid sequences. The hybridization temperature and conditions are critical to ensure the specificity of the interaction between the two strands.

The skull base is the lower part of the skull that forms the floor of the cranial cavity and the roof of the facial skeleton. It is a complex anatomical region composed of several bones, including the frontal, sphenoid, temporal, occipital, and ethmoid bones. The skull base supports the brain and contains openings for blood vessels and nerves that travel between the brain and the face or neck. The skull base can be divided into three regions: the anterior cranial fossa, middle cranial fossa, and posterior cranial fossa, which house different parts of the brain.

Repetitive sequences in nucleic acid refer to repeated stretches of DNA or RNA nucleotide bases that are present in a genome. These sequences can vary in length and can be arranged in different patterns such as direct repeats, inverted repeats, or tandem repeats. In some cases, these repetitive sequences do not code for proteins and are often found in non-coding regions of the genome. They can play a role in genetic instability, regulation of gene expression, and evolutionary processes. However, certain types of repeat expansions have been associated with various neurodegenerative disorders and other human diseases.

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific regions of DNA. It enables the production of thousands to millions of copies of a particular DNA sequence in a rapid and efficient manner, making it an essential tool in various fields such as molecular biology, medical diagnostics, forensic science, and research.

The PCR process involves repeated cycles of heating and cooling to separate the DNA strands, allow primers (short sequences of single-stranded DNA) to attach to the target regions, and extend these primers using an enzyme called Taq polymerase, resulting in the exponential amplification of the desired DNA segment.

In a medical context, PCR is often used for detecting and quantifying specific pathogens (viruses, bacteria, fungi, or parasites) in clinical samples, identifying genetic mutations or polymorphisms associated with diseases, monitoring disease progression, and evaluating treatment effectiveness.

A Schiff base is not a medical term per se, but rather a chemical concept that can be relevant in various scientific and medical fields. A Schiff base is a chemical compound that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, excluding hydrogen. This structure is also known as an azomethine.

The general formula for a Schiff base is R1R2C=NR3, where R1 and R2 are organic groups (aryl or alkyl), and R3 is a hydrogen atom or an organic group. These compounds can be synthesized by the condensation of a primary amine with a carbonyl compound, such as an aldehyde or ketone.

Schiff bases have been studied in various medical and biological contexts due to their potential bioactivities. Some Schiff bases exhibit antimicrobial, antifungal, anti-inflammatory, and anticancer properties. They can also serve as ligands for metal ions, forming complexes with potential applications in medicinal chemistry, such as in the development of new drugs or diagnostic agents.

Bacterial DNA refers to the genetic material found in bacteria. It is composed of a double-stranded helix containing four nucleotide bases - adenine (A), thymine (T), guanine (G), and cytosine (C) - that are linked together by phosphodiester bonds. The sequence of these bases in the DNA molecule carries the genetic information necessary for the growth, development, and reproduction of bacteria.

Bacterial DNA is circular in most bacterial species, although some have linear chromosomes. In addition to the main chromosome, many bacteria also contain small circular pieces of DNA called plasmids that can carry additional genes and provide resistance to antibiotics or other environmental stressors.

Unlike eukaryotic cells, which have their DNA enclosed within a nucleus, bacterial DNA is present in the cytoplasm of the cell, where it is in direct contact with the cell's metabolic machinery. This allows for rapid gene expression and regulation in response to changing environmental conditions.

RNA (Ribonucleic Acid) is a single-stranded, linear polymer of ribonucleotides. It is a nucleic acid present in the cells of all living organisms and some viruses. RNAs play crucial roles in various biological processes such as protein synthesis, gene regulation, and cellular signaling. There are several types of RNA including messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), microRNA (miRNA), and long non-coding RNA (lncRNA). These RNAs differ in their structure, function, and location within the cell.

Adenosine triphosphatases (ATPases) are a group of enzymes that catalyze the conversion of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and inorganic phosphate. This reaction releases energy, which is used to drive various cellular processes such as muscle contraction, transport of ions across membranes, and synthesis of proteins and nucleic acids.

ATPases are classified into several types based on their structure, function, and mechanism of action. Some examples include:

1. P-type ATPases: These ATPases form a phosphorylated intermediate during the reaction cycle and are involved in the transport of ions across membranes, such as the sodium-potassium pump and calcium pumps.
2. F-type ATPases: These ATPases are found in mitochondria, chloroplasts, and bacteria, and are responsible for generating a proton gradient across the membrane, which is used to synthesize ATP.
3. V-type ATPases: These ATPases are found in vacuolar membranes and endomembranes, and are involved in acidification of intracellular compartments.
4. A-type ATPases: These ATPases are found in the plasma membrane and are involved in various functions such as cell signaling and ion transport.

Overall, ATPases play a crucial role in maintaining the energy balance of cells and regulating various physiological processes.

I'm sorry for any confusion, but "thermodynamics" is not a term that has a specific medical definition. It is a branch of physics that deals with the relationships between heat and other forms of energy. However, the principles of thermodynamics can be applied to biological systems, including those in the human body, such as in the study of metabolism or muscle function. But in a medical context, "thermodynamics" would not be a term used independently as a diagnosis, treatment, or any medical condition.

Examples include ethidium bromide and acridine.[citation needed] Mismatched base pairs can be generated by errors of DNA ... kb (= kbp) = kilo-base-pair = 1,000 bp Mb (= Mbp) = mega-base-pair = 1,000,000 bp Gb (= Gbp) = giga-base-pair = 1,000,000,000 ... The GU pairing, with two hydrogen bonds, does occur fairly often in RNA (see wobble base pair). Paired DNA and RNA molecules ... In the human genome, the centimorgan is about 1 million base pairs. An unnatural base pair (UBP) is a designed subunit (or ...
A few or up to thousands of base pairs of the newly synthesized DNA strand can be removed. Mismatch repair is a highly ... Examples of mismatched bases include a G/T or A/C pairing (see DNA repair). Mismatches are commonly due to tautomerization of ... When bound, the MutS2 dimer bends the DNA helix and shields approximately 20 base pairs. It has weak ATPase activity, and ... that recognises the mismatched base on the daughter strand and binds the mutated DNA. MutH binds at hemimethylated sites along ...
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 ... Hunter, William N. (10 April 1986). "Structure of an adenine˙cytosine base pair in DNA and its implications for mismatch repair ... "High-resolution structure of a DNA helix containing mismatched base pairs". Nature. 315 (6020): 694-606. Bibcode:1985Natur.315 ... Savva, Renos (9 February 1995). "The Structural Basis of Specific Base-Excision Repair by Uracil-DNA Glycosylase". Nature. 373 ...
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. Honors and awards received by Modrich include: 1983 ...
Mismatches in DNA base pairing can potentially result in dysfunctional proteins and could lead to cancer. Many DNA polymerases ... 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 ... which acts in detecting base pair mismatches and further performs in the removal of the incorrect nucleotide to be replaced by ...
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 ...
It involves the correction of mismatched base pairs that have been missed by the proofreading element (Klenow fragment) of the ... MutS is a mismatch DNA repair protein, originally described in Escherichia coli. Mismatch repair contributes to the overall ... Nag N, Rao BJ, Krishnamoorthy G (November 2007). "Altered dynamics of DNA bases adjacent to a mismatch: a cue for mismatch ... "The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch". Nature. 407 (6805): 711-7. doi:10.1038/ ...
... the effect of single base pair mismatch". Nucleic Acids Research. 6 (11): 3543-3558. doi:10.1093/nar/6.11.3543. PMC 327955. ... The Illumina Methylation Assay technology takes advantage of ASO to detect one base pair difference (cytosine versus thymine) ... The mismatched ASOs are washed off of the blots, while the matched ASOs (and their labels) remain. In the second diagram, six ... These probes can usually be designed to detect a difference of as little as 1 base in the target's genetic sequence, a basic ...
... 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 will change the codon, potentially replacing an amino acid in a protein. Mutagenesis can help ... 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. ...
... single base pair mismatches, and insertions and deletions at low frequencies. Several such enzymes have been discovered ( ... Surveyor nuclease assay is an enzyme mismatch cleavage assay used to detect single base mismatches or small insertions or ... Enzymatic mismatch cleavage assays exploit the properties of mismatch-specific endonucleases to detect and cleave mismatches. ... All types of mismatches are identifiable by Surveyor nuclease, although the mismatch cutting preferences fall into four groups ...
This finding suggests a mechanism by which polymerases are able to detect incorrect base pairing. Beese had an integral role in ... Through her research, Beese found that the hExo1 enzyme binds the DNA near the site of mismatched pairing, and through ... the enzyme is able to assist in the identification and replacement of incorrect base pairs. By integrating high-resolution X- ... They are using DNA polymerase as a model system to study molecular mechanisms of DNA mis-pair incorporation and action of ...
It can slip at sequence or insert A or C base pairs into a distorted region on DNA strand; ss shown in Figure 3, TLS DNA ... A collection of enzymes from the DNA repair system will come in to excise the mismatch basepair. When these enzymes try to mend ... If the C→U mutation error is detected by its specific glycosylase, the glycosylase will cut the base pair and form an abasic ... The original CG pair will become a TA pair after one round of replication, hence the predominantly seen C→T mutation in ...
... 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, ...
Cleavage of single-basepair mismatches, as a replacement for CEL 1 Nuclease in TILLING. Unidirectional deletion of large DNA ( ... Some is known about its structure, with one exposed Cysteine residue and 3 pairs of disulfide bonds. Some is known about its ... Its ability to recognise double-stranded nucleic acids depends on the base sequence. It tends to cleave at ApN and at T(U) pN. ...
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 ...
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 ...
Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota. ... MsDpo4-a DinB Homolog from Mycobacterium smegmatis-Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches. J ... Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair. Structure. 2005 Oct;13(10): ... Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004 Jul 15;430(6997):377-80. PMID 15254543 ...
... 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 ...
G pair into a T:A pair, effectively changing a base and introducing a mutation. This misincorporated base will not be corrected ... 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 mismatch, it is recorded and the percentage of DNA for which the mismatch is present is noted. This gives the ... Bisulfite-treated DNA is hybridized to probes on "BeadChips." Single-base base extension with labeled probes is used to ...
... 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 ...
... 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 ... base pair. One of the most common base analogs is 5-bromouracil (5BU), the abnormal base found in the mutagenic nucleotide ... which base pairs to cytosine instead of thymine. Cytosine is deaminated to uracil, which base pairs with Adenine instead of ...
DNA mismatch repair (MMR) deficiency: The mismatch repair machinery recognizes and repairs erroneous base pair insertion, ... MUTYH encodes the mutY adenine glycosylase enzyme which excise the mismatched adenine from 8-Oxoguanine:adenine base pairing, ... Taking the information from the 5' and 3' adjacent bases (also called flanking base pairs or trinucleotide context) lead to 96 ... base-pair substitution or substitution point mutation) in one of the 96 mutation types and counting the total number of ...
... and 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 ...
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). ... DNA mismatch repair in any given organism is effected by a suite of mismatch-specific endonucleases. In prokaryotes, this role ...
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 ...
Examples include ethidium bromide and acridine.[citation needed] Mismatched base pairs can be generated by errors of DNA ... kb (= kbp) = kilo-base-pair = 1,000 bp Mb (= Mbp) = mega-base-pair = 1,000,000 bp Gb (= Gbp) = giga-base-pair = 1,000,000,000 ... The GU pairing, with two hydrogen bonds, does occur fairly often in RNA (see wobble base pair). Paired DNA and RNA molecules ... In the human genome, the centimorgan is about 1 million base pairs. An unnatural base pair (UBP) is a designed subunit (or ...
25-61 bases homologous to the target sequence except for a single mismatch to the targeted base, are capable of correcting a ... Base Pair Mismatch / genetics * Base Sequence * CHO Cells * Cricetinae * DNA Repair / genetics* ... 25-61 bases homologous to the target sequence except for a single mismatch to the targeted base, are capable of correcting a ...
The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs ... The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs ... The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs ...
Base Pair Mismatch. *Risk Factors. *DNA Mutational Analysis. *Neoplasm Proteins. *Cell Proliferation ... In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the ... Microsatellite instability (MSI) is an indicator of DNA instability and is caused by abnormalities in DNA mismatch repair (MMR ... Microsatellite instability (MSI) in tumors is diagnostic for inactive DNA mismatch repair. It is widespread among some tumor ...
Base Pair Mismatch. *Biomarkers, Tumor. *Tumor Suppressor Gene. *Neoplasm Invasiveness. *Transfection. *Survival Rate ... METHODS: Expression of p12(CDK2-AP1) protein was examined in 60 pairs of breast cancer specimens and adjacent non-tumor tissues ... We then utilized an in vitro human mismatch repair (MMR) recombinant system to assess for correction of the mutation and ... The precise genetic mechanism of malignant transformation in DNA mismatch repair deficient, microsatellite-unstable colorectal ...
DNA mismatch repair (MMR) is defective in this syndrome. MMR promotes genomic stability by correcting acid-base and small ... Mistakes in base pairing occasionally occur. Some stretches of DNA are more likely to accumulate errors than others, ... This mismatch must be repaired in order to avoid mutations. The DNA mismatch repair system recognizes the DNA mismatch and ... this instability leads to a failure to recognize and repair these nucleotide mismatches. Mismatch repair defects are an early ...
The dual indexes contained a total of 16 base pairs (bp) and were inserted into the flanking regions of the target DNA ... To remove erroneous mismatches around small indels, IndelRealigner was applied to process the alignment of BAM files. ... This latter pair of phylogenies (Machado et al.23 pollinators tree, Ficus PCT tree) reflects a long-held view of the ... Cophylogenetic comparison of each pair of phylogenies of three genomic compartments (a-c) and of the pollinators associated ...
A BACILLUS DNA POLYMERASE I PRODUCT COMPLEX BOUND TO A GUANINE-THYMINE MISMATCH AFTER A SINGLE ROUND OF PRIMER EXTENSION, ... Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that ... Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the ... replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, ...
In contrast, the selection of regulatory mechanisms is independent of the degree of mismatch between a plant miRNA and its ... the degree of base pairing between a miRNA and its target messenger RNA seems to determine whether the regulation occurs ... In animals, the degree of base pairing between a miRNA and its target messenger RNA seems to determine whether the regulation ... In contrast, the selection of regulatory mechanisms is independent of the degree of mismatch between a plant miRNA and its ...
... which rectifies base-pairing errors within the DNA helix. Although a mismatched base pair is a rare occurrence in the DNA helix ... He also showed that mismatch repair plays an important role in the cellular response to certain types of DNA damage and that as ... Modrich established the mechanism of mismatch repair in the bacterium E. coli, and more recently the mechanism by which ... Modrich clarified the nature and functions of mismatch repair, ... are defective in mismatch repair, and he identified the repair ...
In some embodiments, there exist no mismatches (there are all complementary base-pairs). Non-limiting embodiments of a miRNA ... wherein each of the mismatches may be adjacent to at least one complementary base-pair (so that there are not more than 2 ... Thus, miRNAs are capable of silencing the expression of target genes via base-pairing with complementary sequences within mRNA ... Mismatches that are permitted, but are not required, for example, 0, 1 or 2 mismatches between the target and the mature miRNA ...
The mismatches concern a single base pair in the case of a point mutation and several base pairs in the case of an inversion. ... These repeat sequences measure from 10 to 40 base pairs for VNTRs and from 1 to 5 base pairs for STRs. From one individual to ... is a PCR for varietal identification that uses pairs of random primers of reduced size (about 10 base pairs). These primers ... Microsatellites or SSRs (simple sequence repeats) or STRs (short tandem repeats) consist of a few nucleotides-2-6 base pair DNA ...
The third is designing metal complexes that bind at DNA base pair mismatches for possible cancer treatments. Although Bartons ... They also always used well-characterized DNA so they knew how the base pairs stacked and how strongly electron donor and ... In 1993, postdoc Catherine J. Murphy demonstrated that DNA facilitated electron transfer along a 15-base pair DNA duplex-a ... a project to her that involved binding inorganic complexes to DNA such that they would intercalate between the base pairs. "I ...
How is any of what I said a claim when we have enzymes making sure that base pairs are coupled correctly? And every mismatch, ... Amino acid chains have base pairs and trust me, 160 is for a simple protein. We require much complex ones than that. Sure, to ... Therefore, to get a functional strand, you have a probability at every base pair. Apart from that, the "primordial soup" itself ...
Different pair selection methods, different mismatch identification rules and different rule thresholds may produce ... One might base trade exits on profit and loss thresholds rather than a reversion rule. However, the more strategy variations ... A standalone pairs trading strategy appears to require a large inventory of pairs at all times in order to keep capital largely ... A standalone pairs trading strategy of any kind probably requires a large inventory of potential pairs. ...
The E. coli polymerase III α subunit, part of the main replicative polymerase, has a processivity of , 10 base pairs and a ... An explanation for this observation is that upon incorporation of a mismatched base it is more likely that the exonuclease will ... This alignment for catalysis is sensitive to distortions in position caused by incorrect Watson-Crick base pairing, allowing ... Using the base-pairing and active site molecular checkpoints described above, Taq DNA polymerase is incredibly accurate, but ...
Two mismatched base pairs were allowed and the multiple position matching was reported up to 40 alignments using the Tophat ... translation start base was searched for all of the annotated soybean genes (phytozome v9.1). The number of genes was counted ... most translation start base for all of the annotated soy genes was searched (Phytozome v9.1). Sixteen and 76 over-represented ...
The teams analyses of base pairs, DNA mismatches, and nucleic acid quadruplexes are contributing new insights into this realm ... Her group is finding out how making subtle structural changes in hydrogen-bonded base pairs of DNA can impart different σ- and ...
It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase ... DNA mismatch repair protein, C-terminal domain.. Interpro abstract (IPR013507):. This domain is found in MutL and homologues ... Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through ... The dimeric MutL protein has a key function in communicating mismatch recognition by MutS to downstream repair processes. ...
Siddhartha Das and collaborators find a link between DNA base pair mismatches and the location of supercoiling. ... "Coarse-Grained Modelling of DNA Plectoneme Pinning in the Presence of Base-Pair Mismatches." Nucleic Acids Research, DOI: ...
The forward primers were designed to match or mismatch 1 base pair of the EGFR c.2369 C,T (p.T790M); EGFR c.2573 T,G (p.L858R) ... L858R and BRAF V600E alongside mismatching one base pair of each normal genes. All templates for the targets were synthesized ... Surprisingly, the STexS PCR expressed drastic contrasts between matched and mismatched, repressing the mismatched template well ... Optimization for the duplex forming ratio required each dbOligo to be designed at least 10 base pairs and adjusted to elevate ...
A. David, N. Bleimling, C. Beuck, J.-M. Lehn, E. Weinhold, and M.-P. Teulade-Fichou, "DNA mismatch-specific base flipping by a ... due to their sterically difficult intercalation between the base pairs of the double helix; on the other hand, in contrast, ... both for steric reasons and because the length of the linkers does not enable bisintercalation between contiguous base pairs ... S. L. Palumbo, S. W. Ebbinghaus, and L. H. Hurley, "Formation of a unique end-to-end stacked pair of G-quadruplexes in the ...
Positional and neighboring base pair effects on the thermodynamic stability of RNA single mismatches, Biochemistry 49, 8669- ... 2. Znosko, B. M., Burkard, M. E., Schroeder, S. J., Krugh, T. R., and Turner, D. H. (2002) Sheared Aanti×Aanti base pairs in a ... Richardson, K. E. and Znosko, B. M. (2016) "Nearest-neighbor parameters for 7-deaza-adenosine·uridine base pairs in RNA ... and nearest neighbor parameters of pseudouridine-adenosine base pairs in oligoribonucleotides, RNA 19, 1474-1482. ...
Typical guide RNAs have 20 base pairs of homology to the DNA target, but some mismatches are tolerated, particularly on one end ... each of which binds a single base pair, and there is a robust code to address each of the four base pairs (2,3). ... To address a new target, one need only know the Watson-Crick base pairing rules, and the same protein is used for each case. ... Each finger contacts primarily three base pairs of DNA, and there are natural and derived fingers that recognise many of the 64 ...
... shows the structure of the Klenow fragment complexed with a fragment of DNA containing a mismatched terminal base pair. The 3′ ...
This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary ... 10 base pairs [bp]) were analyzed for screening of single-nucleotide variation, including insertion and deletions shorter than ... Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients ... Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients ...
X-ray analysis reveals that a T⋅U mismatch impairs RNA extension by forming a wobble base pair at the Pol II active center that ... RNA base mismatch. Certain mismatches are efficiently formed but impair RNA extension. Other mismatches allow for RNA extension ... The mismatch can also stabilize a paused state of Pol II with a frayed RNA 3′ nucleotide. The frayed nucleotide binds in the ... Structural Basis of Transcription: Mismatch-Specific Fidelity Mechanisms and Paused RNA Polymerase II with Frayed RNA. ...
... methods rely on the specificity and sensitivity of DNA ligases towards mismatch base-pairing to decipher the nucleotide ... In reversible terminator sequencing - pure genomic DNA is first cut into smaller fragments of 100-1000 base pairs. Special ... and the emission wavelength from each DNA cluster is used to identify the base. ...
... and 16 genes involved in mismatch repair, or the re-aligning of complementary base pairs. Interestingly, the team found that ...

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