Mismatches in dna. Medical search. Frequent questions

The single-strand gap created by the exonuclease can then be repaired by DNA Polymerase III (assisted by single-strand-binding protein), which uses the other strand as a template, and finally sealed by DNA ligase. (wikipedia.org)
Schließlich fügt die DNA-Polymerase die richtigen Nukleotide hinzu und die DNA-Ligase verschließt die Lücken an den Kanten und repariert den Fehler. (jove.com)
Trotz der Korrekturfähigkeit der DNA-Polymerase tritt etwa alle 1 Million Basenpaare ein Kopierfehler auf. (jove.com)
One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favoring subsequent mismatch excision. (rcsb.org)
Here we a present a structural characterization of all 12 possible mismatches captured at the growing primer terminus in the active site of a polymerase. (rcsb.org)
Our observations suggest four mechanisms that lead to mismatch-induced stalling of the polymerase. (rcsb.org)
These lesions miscode in DNA polymerase I-mediated DNA synthesis in vitro5 and are known to be mutagenic in vivo6. (umassmed.edu)
Reference: Mismatched and matched dNTP incorporation by DNA polymerase beta proceed via analogous kinetic pathways. (neb.com)
While matched nucleotide incorporation by DNA polymerase beta (Pol beta) has been well-studied, a true understanding of polymerase fidelity requires comparison of both matched and mismatched dNTP incorporation pathways. (neb.com)
Here we report on a simple and highly accessible approach to convert commercially available customized DNA microarrays of any complexity and density to RNA microarrays via a T7 RNA polymerase-mediated extension of photocrosslinked methyl RNA primers and subsequent degradation of the DNA templates. (nature.com)
The resulting RNA stays attached to the surface since the RNA polymerase remains stalled on the DNA template at the terminal biotin-streptavidin roadblock. (nature.com)
High-throughput sequencing-RNA affinity profiling (HiTS-RAP) 22 is conceptually similar to RNA-MaP, but uses the E. coli replication terminator protein Tus to stall the RNA polymerase after transcribing the variable section of the DNA library. (nature.com)
The enzymes remove the damaged base forming an AP site which is repaired by AP endonuclease before the nucleotide gap in the DNA strand is filled by DNA polymerase. (news-medical.net)
The process involves the recognition of damage which is then cleaved on both sides by endonucleases before resynthesis by DNA polymerase. (news-medical.net)
The third excision mechanism is called mismatch repair and occurs when mismatched bases are incorporated into the DNA strand during replication and are not removed by proofreading DNA polymerase. (news-medical.net)
This shape mimicry enables the mismatch to evade the error detection mechanisms of the polymerase, which would normally either prevent mismatch incorporation or promote its nucleolytic excision. (rcsb.org)
2022. Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ε. (nih.gov)
DNA Polymerase and Mismatch Repair Exert Distinct Microsatellite Instability Signatures in Normal and Malignant Human Cells. (bvsalud.org)

We have shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a topoisomerase II inhibitor. (aacrjournals.org)
Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause the dominant adult cancer syndrome termed Lynch syndrome or hereditary non-polyposis colorectal cancer. (nih.gov)
Mutations in genes of the DNA mismatch repair system (MMR) are strongly linked to the development of hereditary non-polyposis colorectal cancer and play a significant role in sporadic cancer too. (uni-luebeck.de)
This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). (jnccn.org)
DNA mismatch repair (MMR) is essential in the surveillance of accurate transmission of genetic information, and defects in this pathway lead to microsatellite instability and hereditary non-polyposis colorectal cancer (HNPCC). (elsevierpure.com)
LS involves mutations in DNA mismatch repair genes with markedly increased risk for colorectal cancer. (cdc.gov)

The first evidence for mismatch repair was obtained from S. pneumoniae (the hexA and hexB genes). (wikipedia.org)
The MLH1 , MSH2 , MSH6 , and PMS2 genes are involved in repairing errors that occur when DNA is copied in preparation for cell division (a process called DNA replication ). (medlineplus.gov)
Because these genes work together to fix DNA errors, they are known as mismatch repair (MMR) genes. (medlineplus.gov)
Variants in any of these genes prevent the proper repair of DNA replication errors. (medlineplus.gov)
Introduction: Lynch syndrome-associated cancer develops due to germline pathogenic variants in one of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 or PMS2. (lu.se)
Polymorphisms in DNA repair genes and susceptibility to primary intracranial brain gliomas. (cdc.gov)
One of her current research projects is aimed to examine associations between germline pathogenic variants in mismatch-repair (MMR) genes and CAG-repeats in HTT, and how errors in MMR-genes effect somatic CAG-repeat expansions. (lu.se)
The role of DNA mismatch repair genes for Huntington disease. (lu.se)

DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintains genomic integrity and MMR-deficient cells show an increased mutation rate. (oncotarget.com)
Nevertheless, it appears that mismatch correction at m6G residues in DNA does not lead to reduced induction of mutation by MNNG. (umassmed.edu)
Replacement of a homologous Pms1 residue has a much smaller effect on mutation rate and does not reduce DNA binding. (nebraska.edu)
Damage to DNA is caused by the incorporation of incorrect nucleotide bases during DNA replication and the chemical changes caused by spontaneous mutation or exposure to environmental factors such as radiation. (news-medical.net)

DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage. (wikipedia.org)
Topoisomerases are nuclear enzymes that modify the topological state of DNA and participate in fundamental metabolic processes such as replication, transcription, repair, recombination, and chromosome segregation (1) . (aacrjournals.org)
Scholars@Duke publication: A 'Semi-Protected Oligonucleotide Recombination' Assay for DNA Mismatch Repair in vivo Suggests Different Modes of Repair for Lagging Strand Mismatches. (duke.edu)
Here, we have developed a new assay that uniquely allows us to introduce targeted 'mismatches' directly into the replication fork via oligonucleotide recombination, examine the directionality of MMR, and quantify the nucleotide-dependence, sequence context-dependence, and strand-dependence of their repair in vivo-something otherwise nearly impossible to achieve. (duke.edu)
Here, we report positional cloning of Pairing homoeologous 2 (Ph2) and functional validation of the wheat DNA mismatch repair protein MSH7-3D as a key inhibitor of homoeologous recombination, thus solving a half-century-old question. (nature.com)
Homologous recombination involves the exchange of nucleotide sequences to repair damaged bases on both strands of DNA through the utilization of a sister chromatid. (news-medical.net)
Homologous recombination involves the precise exchange of similar or identical nucleic acid sequences between two DNA molecules. (cshlpress.com)
Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of recombinational DNA repair, meiotic recombination, and the regulation of these processes. (cshlpress.com)
This volume is an indispensable reference for biochemists, molecular biologists, and cell biologists who want to understand how DNA recombination maintains genomic integrity in individual organisms and across generations. (cshlpress.com)
Enzymes in base excision (BER), nucleotide excision (NER), double strand break/recombination (DSB/RR), mismatch (MMR), and direct-damage DNA repair pathways are important in the repair of diverse types of DNA damage. (cdc.gov)

In Escherichia coli, a DNA mismatch repair (MMR) pathway corrects errors that occur during DNA replication by coordinating the excision and re-synthesis of a long tract of the newly-replicated DNA between an epigenetic signal (a hemi-methylated d(GATC) site or a single-stranded nick) and the replication error after the error is identified by protein MutS. (duke.edu)
Nucleotide excision repair is a widespread mechanism for repairing damage to DNA and recognizes multiple damaged bases. (news-medical.net)

The damage is repaired by recognition of the deformity caused by the mismatch, determining the template and non-template strand, and excising the wrongly incorporated base and replacing it with the correct nucleotide. (wikipedia.org)
The removal process involves more than just the mismatched nucleotide itself. (wikipedia.org)
sgRNAs with +67 or +85 nucleotide (nt) tracrRNA tails mediated DNA cleavage at all target sites tested, with up to fivefold higher levels of indels than the corresponding crRNA-tracrRNA duplexes ( Fig. 1b and Supplementary Fig. 1a ). (cdc.gov)

The gene products are, therefore, called the "Mut" proteins, and are the major active components of the mismatch repair system. (wikipedia.org)
Three of these proteins are essential in detecting the mismatch and directing repair machinery to it: MutS, MutH and MutL (MutS is a homologue of HexA and MutL of HexB). (wikipedia.org)
In addition to an established role in the repair of postreplicative DNA errors, DNA mismatch repair (MMR) proteins also contribute to cellular responses to exogenous DNA damage. (qxmd.com)
In combination with previously established roles for MMR proteins in response to UVB-induced DNA damage, our data point towards an expanded perspective of the importance of MMR proteins in the suppression of UVB-induced tumorigenesis and, potentially, tumour behaviour. (qxmd.com)
Proteins of the MMR are necessary for the induction of apoptosis in response to non-tolerable amounts of DNA damage. (uni-luebeck.de)
They also discuss how these proteins and pathways are strictly regulated to avoid genomic instability, which can lead to diseases such as cancer, and how they are coordinated with other nuclear processes (e.g., transcription and DNA replication). (cshlpress.com)
Usually, the NOE and NMRD in B-DNA is expected to be less ``integral'' than methods can only provide bounds on the residence water molecules buried inside proteins. (lu.se)

MutS forms a dimer (MutS2) that recognises the mismatched base on the daughter strand and binds the mutated DNA. (wikipedia.org)
MutH binds at hemimethylated sites along the daughter DNA, but its action is latent, being activated only upon contact by a MutL dimer (MutL2), which binds the MutS-DNA complex and acts as a mediator between MutS2 and MutH, activating the latter. (wikipedia.org)
Upon activation by the MutS-DNA complex, MutH nicks the daughter strand near the hemimethylated site. (wikipedia.org)
The crystal structure of MutS reveals that it is exceptionally asymmetric, and, while its active conformation is a dimer, only one of the two halves interacts with the mismatch site. (wikipedia.org)
We find that repair of genomic lagging strand mismatches occurs bi-directionally in E. coli and that, while all MutS-recognized mismatches had been thought to be repaired in a consistent manner, the directional bias of repair and the effects of mutations in MutS are dependent on the molecular species of the mismatch. (duke.edu)

Accurate DNA replication is essential for genomic stability. (rcsb.org)
Changes to the structure of DNA can cause mutations and genomic instability, leading to cancer. (news-medical.net)
The repair of damage to both DNA strands is particularly important in maintaining genomic integrity. (news-medical.net)
To explore the associations of genomic alterations identified in cell-free (cf)DNA with DFS in patients treated with FOLFOX with or without atezolizumab. (clinicaltrialsgps.com)
Her translational research interests use of real time genomic profiling to identify novel therapeutic strategies for gastrointestinal cancers, identification of non coding alterations as modifiers of the DNA damage response pathway and generation of organoid models of cancer as a tool for precision oncology as a member of the PRECODE consortium. (tcd.ie)
Download DNA or protein sequence, view genomic context and coordinates. (yeastgenome.org)

MutL recruits UvrD helicase (DNA Helicase II) to separate the two strands with a specific 3' to 5' polarity. (wikipedia.org)

In stopped-flow, a biphasic fluorescence trace is observed for both enzymes during mismatched dNTP incorporation. (neb.com)
Pre-steady-state kinetic evaluation reveals that both enzymes display similar correct dNTP insertion profiles, and the lower fidelity intrinsic to the I260Q mutant results from enhanced efficiency of mismatched incorporation. (neb.com)
In mismatch repair, the missed errors are later corrected by enzymes which recognize and excise the mismatched base to restore the original sequence. (news-medical.net)

For both WT and I260Q mismatched dNTP incorporation, the rate of the fast phase, reflecting subdomain closing, is comparable to that induced by correct dNTP. (neb.com)
2022. Ribonucleotide incorporation by eukaryotic B-family DNA replicases and its consequences. (nih.gov)

Escherichia coli has a correction system which removes mismatched bases from DNA1. (umassmed.edu)

As a result, the MSH2 gene's role in DNA repair is impaired, which can lead to accumulated DNA errors and cancer development. (medlineplus.gov)

Mismatch repair is strand-specific. (wikipedia.org)
During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. (wikipedia.org)
In order to begin repair, the mismatch repair machinery distinguishes the newly synthesised strand from the template (parental). (wikipedia.org)
It is suspected that, in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate strand. (wikipedia.org)
Loaded PCNA then directs the action of the MutLalpha endonuclease to the daughter strand in the presence of a mismatch and MutSalpha or MutSbeta. (wikipedia.org)
A few or up to thousands of base pairs of the newly synthesized DNA strand can be removed. (wikipedia.org)
The entire MutSHL complex then slides along the DNA in the direction of the mismatch, liberating the strand to be excised as it goes. (wikipedia.org)
DNA methylase then rapidly methylates the daughter strand. (wikipedia.org)
Hi Xiang, I try to generate a PDB file using double strand DNA sequence, but the G-T base pair is converted into A-T base pair automatically when I use w3DNA. (x3dna.org)
The non-defective strand is used as a template with the damaged DNA on the other strand removed and replaced by the synthesis of new nucleotides. (news-medical.net)

Mutants (dam) which lack the major DNA adenine methylase2 are hypersensitive to the effects of base analogue mutagens such as 2-aminopurine3 and appear to be defective in mismatch correction. (umassmed.edu)

Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer terminus. (rcsb.org)
Even though high-fidelity polymerases copy DNA with remarkable accuracy, some base-pair mismatches are incorporated at low frequency, leading to spontaneous mutagenesis. (rcsb.org)

Evidence that dysregulated DNA mismatch repair characterizes human nonmelanoma skin cancer. (qxmd.com)

These results suggest that mismatch correction occurs at m6G residues in DNA. (umassmed.edu)

Examples of mismatched bases include a G/T or A/C pairing (see DNA repair). (wikipedia.org)
Mismatches are commonly due to tautomerization of bases during DNA replication. (wikipedia.org)
Methylation of guanine bases produces a change in the structure of DNA by forming a product that is complimentary to thymine rather than cytosine. (news-medical.net)
Movement of a single proton on one of the mismatched bases alters the hydrogen-bonding pattern such that a base pair forms with an overall shape that is virtually indistinguishable from a canonical, Watson-Crick base pair in double-stranded DNA. (rcsb.org)

Seventy-two samples had sufficient DNA for the sequencing-based MSI assay, of which 55 (76.4%) and 61 (84.7%) scored as MSI-high using the 24-marker and 54-marker panels, respectively. (lu.se)
Using the SURVEYOR nuclease assay 13 , we assessed the ability of each Cas9-sgRNA complex to generate indels in human embryonic kidney (HEK) 293FT cells through the induction of DNA doublestranded breaks (DSBs) and subsequent nonhomologous end joining (NHEJ) DNA damage repair (Online Methods). (cdc.gov)

The DNA is looped out to search for the nearest d(GATC) methylation site to the mismatch, which could be up to 1 kb away. (wikipedia.org)
We also show that SpCas9-mediated cleavage is unaffected by DNA methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize off-target modification. (cdc.gov)

The fact that the damage detection and repair systems are as complex as the replication machinery itself highlights the importance evolution has attached to DNA fidelity. (wikipedia.org)
Overall, our results provide first direct evidence that mismatched and matched dNTP incorporations proceed via analogous kinetic pathways, and support our standing hypothesis that the fidelity of Pol beta originates from destabilization of the mismatched closed ternary complex and chemical transition state. (neb.com)

DNA encodes the cell genome and is therefore a permanent copy of a structure necessary for the correct functioning of a cell. (news-medical.net)

Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that long-range distortions in the DNA transmit the presence of the mismatch back to the enzyme active site, suggesting the structural basis for the short-term memory of replication errors. (rcsb.org)

For each DNA repair pathway, multivariate logistic analyses included all polymorphisms in the pathway plus ever/never living on a farm and ever/never smoking, as surrogates for occupational and environmental exposure. (cdc.gov)

Classical nonhomologous end joining connects the break ends without a homologous template through the use of short DNA sequences called microhomologies. (news-medical.net)
Buehl CJ, Goff NJ, Hardwick SW, Gellert M, Blundell TL, Yang W, Chaplin AK , Meek K. Two distinct long-range synaptic complexes promote different aspects of end processing prior to repair of DNA breaks by non-homologous end joining. (le.ac.uk)

Any mutational event that disrupts the superhelical structure of DNA carries with it the potential to compromise the genetic stability of a cell. (wikipedia.org)
However, an important challenge still facing breeders now is the ability to routinely perform DNA-introgression, a process by which distantly related chromosomes exchange genetic information that is passed onto progeny. (nature.com)
2003 ). DNA barcodes can provide information on genetic variation within and between species, rapidly assign taxonomic status across divergent lineages (Hebert and Gregory 2005 ), and identify the prey composition of predators' gut contents (Agustí et al. (springer.com)
This process directs the repair of many DNA lesions in somatic cells and generates genetic variation in sperm and egg cells during meiosis. (cshlpress.com)

In conclution, DNA amplification is a rapid, reliable and accurate method with a high degree of sensitivity and specificity for the detection of Mycobacterium tuberculosis DNA sequences and it can replace the conventional culture method in the diagnosis of extra pulmonary tuberculosis and tuberculosis meningitis except in the situation when antibiotic sensitivity results are required. (who.int)

DNA repair can be divided into a set of mechanisms that identify and correct damage in DNA molecules. (news-medical.net)

This phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. (clinicaltrialsgps.com)

The yeast Mlh1-Pms1 heterodimer required for mismatch repair (MMR) binds to DNA. (nebraska.edu)
Here we map DNA binding to N-terminal fragments of Mlh1 and Pms1. (nebraska.edu)
We demonstrate that Mlh1 and Pms1 N-terminal domains (NTDs) independently bind to double-stranded and single-stranded DNA, in the absence of dimerization and with different affinities. (nebraska.edu)
These substitutions strongly reduce DNA binding by the Mlh1 NTD and, to a lesser extent, they also reduce DNA binding by full-length Mlh1 and the Mlh1-Pms1 heterodimer. (nebraska.edu)
The results demonstrate that NTDs of yeast Mlh1 and Pms1 contain independent DNA binding sites and they suggest that the C-terminal region of Mlh1p may also contribute to DNA binding. (nebraska.edu)
The differential mutator effects and binding properties observed here further suggest that Mlh1 and Pms1 differ in their interactions with DNA. (nebraska.edu)
Finally, the results are consistent with the hypothesis that DNA binding by Mlh1 is important for MMR. (nebraska.edu)

In the last two decades, DNA barcoding, the sequencing of short species-specific amplicons, has considerably simplified community analyses (Hebert et al. (springer.com)

The syn-conformation of the guanine base of the mismatch is stabilised by hydrogen bonding to a network of solvent molecules in both the major and minor grooves. (ox.ac.uk)

When bound, the MutS2 dimer bends the DNA helix and shields approximately 20 base pairs. (wikipedia.org)
The DNA mismatch repair (MMR) system is involved in the correction of base/base mismatches and insertion/deletion loops arising during replication. (aacrjournals.org)
The structure of the synthetic dodecamer d(CGCAAATTGGCG) has been shown by single crystal X-ray diffraction methods to be that of a B-DNA helix containing two A(anti).G(syn) base pairs. (ox.ac.uk)
The refinement, based on data to a resolution of 2.25 A shows that the mismatch base pairs are held together by two hydrogen bonds. (ox.ac.uk)
May you please guide me that how can I convert the DNA helix contained GT base pair to PDB files? (x3dna.org)
The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs. (wakehealth.edu)
Gmeiner WH, Salsbury F, Olsen CM, Marky LA. The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs. (wakehealth.edu)

Structural and thermodynamic studies on the adenine.guanine mismatch in B-DNA. (ox.ac.uk)
Unlike DNA, which mostly exists as double-stranded structures that are well defined and exhibit low structural and binding diversity, RNA is typically single-stranded and naturally assumes complex three-dimensional structures. (nature.com)

I. To determine whether atezolizumab combined with oxaliplatin, leucovorin calcium, and fluorouracil (FOLFOX) and its continuation as monotherapy can significantly improve disease-free survival (DFS) compared to FOLFOX alone in patients with stage III colon cancers and deficient DNA mismatch repair (dMMR). (clinicaltrialsgps.com)
DNA mismatch repair (MMR) deficiency syndrome, also referred to as the recessive form of Turcot syndrome, is characterized by childhood onset of CNS tumors, hematologic malignancies, colorectal cancers, and NF1-like cutaneous lesions. (aku.edu)

The Hanks Surname Y-DNA Project, created in 2002, seeks to identify the lines of present day Hanks, Hancks and variants and, together with genealogy research, determine how they are related to one another. (familytreedna.com)
Variants in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. (medlineplus.gov)

Y-DNA - To learn more about your paternal lineage, Family Tree DNA (FTDNA) tests the Y-chromosome which is passed from father to son to son, etc. (familytreedna.com)

Direct reversal of DNA damage is a mechanism of repair that does not require a template and is applied to two main types of damage. (news-medical.net)
UV light induces the formation of pyrimidine dimers which can distort the DNA chain structure, blocking transcription beyond the area of damage. (news-medical.net)
The damage caused by alkylating agents reacting with DNA can also be repaired through direct reversal. (news-medical.net)
High doses of radiation damage to talk to your doctor about not only what will happen cancer cells' DNA, causing them to die over time. (medlineplus.gov)

Because MMR is assumed to modulate cytotoxicity to various chemotherapeutic agents that act upon DNA, our objectives have been to define its possible involvement in the cytotoxicity of topoisomerase inhibitors. (aacrjournals.org)

If, however, the nick is on the 3' end of the mismatch, ExoI (a 3' to 5' enzyme) is used. (wikipedia.org)

East Asia is an important contributor to influenza surveillance but often has mismatch between vaccine and contemporarily circulating strains. (cdc.gov)

coli werden spezifische DNA- Sequenzen methyliert, nach der DNA-Synthese wird eine Methylgruppe hinzugefügt und der neue Strang identifiziert. (jove.com)
We report here that E. coli dam mutants are also sensitive to the DNA methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which introduces O6-methylguanine (m6G) into the DNA. (umassmed.edu)

October 21, 2015: New study of the matrilineal kin of Abraham Lincoln's mother Nancy Hanks has demonstrated that Lincoln's mitochondrial DNA belonged to a very rare haplogroup X1c, and has provided evidence of the maternal ancestry of Nancy Hanks Lincoln. (familytreedna.com)

DNA is probably analogous to the internal hy- pancreatic trypsin inhibitor. (lu.se)

The sensitivity of the PCR method is largely dependent on the efficiency of the DNA extraction procedure which, could probably be improved by modifications of the lysis technique. (who.int)

Autosomal DNA - Approximately 1/2 of your Autosomal DNA is received randomly from each of your parents. (familytreedna.com)

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