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MLH1
DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the ''MLH1'' gene located on chromosome 3. The gene is commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 have also been studied in other organisms including mouse and the budding yeast ''Saccharomyces cerevisiae''. Function Variants in this gene can cause hereditary nonpolyposis colon cancer (Lynch syndrome). It is a human homolog of the ''E. coli'' DNA mismatch repair gene, mutL, which mediates protein-protein interactions during mismatch recognition, strand discrimination, and strand removal. Defects in MLH1 are associated with the microsatellite instability observed in hereditary nonpolyposis colon cancer. Alternatively spliced transcript variants encoding different isoforms have been described, but their full-length natures have not been determined. Role in DNA mismatch repair MLH1 protein is one component of a system of seven ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
DNA Mismatch Repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of nucleobase, bases that can arise during DNA replication and Genetic recombination, recombination, as well as DNA repair, repairing some forms of DNA damage. Mismatch repair is strand-specific. During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. In order to begin repair, the mismatch repair machinery distinguishes the newly synthesised strand from the template (parental). In gram-negative bacteria, transient methylase, hemimethylation distinguishes the strands (the parental is methylated and daughter is not). However, in other prokaryotes and eukaryotes, the exact mechanism is not clear. It is suspected that, in eukaryotes, newly synthesized lagging-strand DNA transiently contains Nick (DNA), nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
PMS2
Mismatch repair endonuclease PMS2 (postmeiotic segregation increased 2) is an enzyme that in humans is encoded by the ''PMS2'' gene. Function This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human PMS2 related genes are located at bands 7p12, 7p13, 7q11, and 7q22. Exons 1 through 5 of these homologues share high degree of identity to human PMS2 The product of this gene is involved in DNA mismatch repair. The protein forms a heterodimer with MLH1 and this complex interacts with MSH2 bound to mismatched bases. Defects in this gene are associated with hereditary nonpolyposis colorectal cancer, with Turcot syndrome, and are a cause of supratentorial primitive neuroectodermal tumors. Alternatively spliced transcript variants have been observed. Mismatch repair and endonuclease activity PMS2 is involved in mismatch repair and is known to have latent endonuclease activity that depends on the integrity of the meta-binding motif in Mut ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Cancer Epigenetics
Cancer epigenetics is the study of epigenetics, epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than mutation, genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of gene expression, expression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG site#Methylation, silencing, cancer, and aging, CpG islands) than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 Genetic hitchhiking, hitchhiker or passenger mutations. However ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.'' ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, such as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word neoplasm is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
MSH2
DNA mismatch repair protein Msh2 also known as MutS homolog 2 or MSH2 is a protein that in humans is encoded by the ''MSH2'' gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes for a DNA mismatch repair (MMR) protein, MSH2, which forms a heterodimer with MSH6 to make the human MutSα mismatch repair complex. It also dimerizes with MSH3 to form the MutSβ DNA repair complex. MSH2 is involved in many different forms of DNA repair, including transcription-coupled repair, homologous recombination, and base excision repair. Mutations in the MSH2 gene are associated with microsatellite instability and some cancers, especially with hereditary nonpolyposis colorectal cancer (HNPCC). At least 114 disease-causing mutations in this gene have been discovered. Clinical significance Hereditary nonpolyposis colorectal cancer (HNPCC), sometimes referred to as Lynch syndrome, is inherited in an autosomal dominant fashio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Hereditary Nonpolyposis Colorectal Cancer
Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary predisposition to colon cancer. HNPCC includes (and was once synonymous with) Lynch syndrome, an autosomal dominant genetic condition that is associated with a high risk of colon cancer, endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited genetic mutations that impair DNA mismatch repair. It is a type of cancer syndrome. Other HNPCC conditions include Lynch-like syndrome, polymerase proofreading-associated polyposis and familial colorectal cancer type X. Signs and symptoms Risk of cancer ''Lifetime risk and mean age at diagnosis for Lynch syndrome–associated cancers'' In addition to the types of cancer found in the chart above, it is understood that Lynch syndrome also contributes to an increased risk of small bowel cancer, pancreatic cancer, ureter/renal pelvis cancer, b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
MLH3
DNA mismatch repair protein Mlh3 is a protein that in humans is encoded by the ''MLH3'' gene. Function This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. Orthologs of human MLH3 have also been studied in other organisms including mouse and the budding yeast ''Saccharomyces cerevisiae''. Meiosis In addition to its role in DNA mismatch repair, MLH3 protein is also involved in meiotic crossing over. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
PMS1
PMS1 protein homolog 1 is a protein that in humans is encoded by the ''PMS1'' gene. Function The protein encoded by this gene was identified by its homology to a yeast protein involved in DNA mismatch repair. A role for this protein in mismatch repair has not been proven. However, the protein forms heterodimers with MLH1, a DNA mismatch repair protein, and some cases of hereditary nonpolyposis colorectal cancer have been found to have mutations in this gene. Yeast studies In the yeast ''Saccharomyces cerevisiae'', the MSH2, MLH1 and PMS1 proteins are required for repair of DNA base pair mismatches, thus contributing to mutation avoidance. The MLH1 and PMS1 proteins physically associate, likely forming a heterodimer which then interacts with the MSH2 protein to form a ternary complex that acts in the initiation of DNA mismatch repair. The nucleotide sequence of the ''PMS1'' gene from ''S. cerevisiae'' has a 2,712-base pair open reading frame and a predicted molecular mass of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Exonuclease 1
Exonuclease 1 is an enzyme that in humans is encoded by the ''EXO1'' gene. This gene encodes a protein with 5' to 3' exonuclease activity as well as RNase activity (endonuclease activity cleaving RNA on DNA/RNA hybrid). It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in DNA mismatch repair and homologous recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. Meiosis ExoI is essential for meiotic progression through metaphase I in the budding yeast ''Saccharomyces cerevisiae'' and in mouse. Recombination during meiosis is often initiated by a DNA double-strand break (DSB) as illustrated in the accompanying diagram. During recombination, sections of DNA at the 5' ends of the break are cut away in a process called ''resection''. In the ''strand invasion'' step that follows, an overhanging 3' end of the broken DNA molecule "invades" the DNA of a homologous chr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Microsatellite Instability
Microsatellite instability (MSI) is the condition of genetic hypermutability (predisposition to mutation) that results from impaired DNA mismatch repair (MMR). The presence of MSI represents phenotypic evidence that MMR is not functioning normally. MMR corrects errors that spontaneously occur during DNA replication, such as single base mismatches or short insertions and deletions. The proteins involved in MMR correct polymerase errors by forming a complex that binds to the mismatched section of DNA, excises the error, and inserts the correct sequence in its place. Cells with abnormally functioning MMR are unable to correct errors that occur during DNA replication and consequently accumulate errors. This causes the creation of novel microsatellite fragments. Polymerase chain reaction-based assays can reveal these novel microsatellites and provide evidence for the presence of MSI. Microsatellites are repeated sequences of DNA. These sequences can be made of units of 1 to 6 bas ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
MSH6
MSH6 or mutS homolog 6 is a gene that codes for DNA mismatch repair protein Msh6 in the budding yeast ''Saccharomyces cerevisiae''. It is the homologue of the human "G/T binding protein," (GTBP) also called p160 or hMSH6 (human MSH6). The MSH6 protein is a member of the Mutator S (MutS) family of proteins that are involved in DNA damage repair. Defects in hMSH6 are associated with atypical hereditary nonpolyposis colorectal cancer not fulfilling the Amsterdam criteria for HNPCC. hMSH6 mutations have also been linked to endometrial cancer and the development of endometrial carcinomas. Discovery MSH6 was first identified in the budding yeast ''S. cerevisiae'' because of its homology to MSH2. The identification of the human GTBP gene and subsequent amino acid sequence availability showed that yeast MSH6 and human GTBP were more related to each other than any other MutS homolog, with a 26.6% amino acid identity. Thus, GTBP took on the name human MSH6, or hMSH6. Structure In the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
