Mismatch repair (MMR) system is critical to maintaining the overall Integrity of the genetic material, and the main features of this system. It is stored in the course of a highly evolved. MMR system is well-known for his role best. Located on the lower level acceptable repair after replication of DNA polymerization errors is important in order to maintain the mutation. In addition to the recognition replicationgenerated mismatch, also MMR proteins, but it is only intended to correct the mismatch in the hetero.

Recombination intermediates. Mismatch recognition in recombinant intermediates can induce the repair process leading to genetic transformation the gene is found Can cause anti-recombinant activity to prevent recombination events to go to completion or event,. Anti-recombination activity of MMR. Protein promotes genomic stability by suppressing the reaction between the divergent Sequences from different organisms, or present in the genome of a single. In addition to recognition and processing of DNA mismatch, including Äúnormal, the AU, The base MMR system, I play a role in response to DNA damage. In the end, MMR eukaryotic proteins have, recombination of roles not related to non-compliance Protein and some identification, have evolved an important role in the metabolism meiotic chromosome. This assessment summarizes the different roles of MMR proteins. To promote genetic stability, we are focused on the impact of MMR of genetic defect.

The (MMR), 2 (PMS2) protein that is also known as PMS1 protein homolog 2, separation meiosis after increased the DNA mismatch repair. Members of PMS2 gene family has been found in a cluster of seven on chromosome. Protein of PMS2 96 kDa is PMS1, and MLH1, MLH3 mismatch repair closely related is the homolog of gene Mutl of bacteria. Coordinate bond This complex of other proteins, PMS2 protein heterodimers with proteins MLH1 that are activated in the presence of ATP to repair errors that occurred during cell preparation of DNA for cell division I will form a.

Loss of PMS2 expression in tumors, can determine the suitability for mutation analysis is useful in identifying a mutation carrier hMLH1. The defect account of PMS2 gene for a significant proportion of tumor microsatellite instability and, for a significant percentage of small but colon cancer. Dominant genetic disorder associated with changes in the HNPCC syndrome known as Turcot syndrome, hereditary colon cancer, nonpolyposis (HNPCC) is clearly too much, PMS2 is associated with.

Nonpolyposis, also known as Lynch syndrome (HNPCC) is an autosomal that the colon, uterus, stomach, as well as upper urinary tract, and predispose individuals to the development of other cancers also, colon cancer is hereditary is a dominantly inherited cancer syndrome. People with HNPCC / Lynch syndrome, have a germline mutation in one of several genes involved in DNA mismatch repair. Most of the mutations that are associated with the occurrence HNPCC / Lynch syndrome in the MLH1 and MSH2, but mutation of PMS2 and MSH6 have also been identified.

There are family history and / or personal, some strategies for individuals to evaluate a measure of HNPCC / Lynch syndrome cancer. Typically, the first step, the HNPCC / Lynch syndrome involving loss of protein expression of one or more and (the presence of a set of types changes repetitive DNA called microsatellites) Microsatellite instability genes associated with HNPCC / Lynch syndrome is to evaluate tumor characteristics common to people with.

Immunohistochemistry microsatellite instability and (MSI) (IHC), is interpreted together in order to assess the risk of HNPCC / Lynch syndrome generally. This suggests a defect DNA mismatch repair high level of MSI in the tumor, but this knowledge does not provide a gene information involved. Used to evaluate the protein PMS2 in HNPCC / Lynch expression of MLH1, and MSH2, MSH6,, test strategy, IHC is a cancer-related syndrome further. Loss of expression of one or more of these proteins in tumors, it will be useful to identify that it should be analyzed genes associated with mutations of interest (s). IHC and MSI are read together, but they also, separately in order to respond to the clinical situation in which barriers to be run these tests at the same time (for example, financial problems, requirements of the sample) and is present are available.

You can determine the loss or retention of PMS2 protein expression and MLH1, MSH2, MSH6 in IHC alone. When the protein all four are present as approximately 5% of the tumors that display MSI with normal expression of the four proteins these genes, potential HNPCC / Lynch syndrome is reduced but not eliminated. Loss of protein in one or more of IHC shows the probability of HNPCC / Lynch syndrome is increased and DNA mismatch repair of incomplete tumor. Germ cell test Each gene (s) (i.e., mutation analysis) it is possible for to identify germline mutations cause, is performed in order to enable testing of individuals predicted risk.

The integrity of the genome of the organism of all, I was threatened of nature in the e-mail constantly. (For example, production environmental pollutants, the endogenous reactive metabolite) chemical ultraviolet (UV) light, ionizing radiation and] damaged DNA of the agent. The number of complex nature, has developed a multi-protein repair process having a substrate specificity overlapping large part to overcome the adverse effects of DNA damage. In contrast, shows high substrate specificity removing method lesions without errors essentially cells, sugar – in simple system identified as very reversal of direct DNA damage dependent protein does not contain cleavage of phosphate , base excision or backbone can be used to repair. Repair of dioxygenase (I) and alkylation damage alkyl transferase, and repair damage caused by ultraviolet (II) in the photolyases and light product of spore lyase: In a brief review of these two types of direct reversal of DNA damage I offer.

Most cases of DNA damage was not reversible. For the case is reversible, damage, to remove the base, our body is using an inverted repair mechanism directly. Repair direct reversal repair mechanism of damage repair the lesion or area by direct protein professional of our bodies. Also, is the simplest form of DNA repair, this is how most energy-efficient. In contrast to the others, it does not require a reference template single-stranded repair mechanism. Further, it does not include the step of decomposing the phosphodiester backbone of DNA. Examples of reversible DNA damage repair repair and using direct alkylation can be repaired by direct removal of the alkyl group. Alkylating agents, can be alkylated DNA into the body of carcinogenicity. Creating a drug (eg, treatment leukemia, tumors), which is used for industrial chemical widely. Leads to pairing DNA bases are alkylated incorrectly, leading to cell death in the end.

Examples of alkyl include, but are methylated is added methyl group of the guanine nucleotide (CH 3) in (G). Instead, I bring cytosine (C), and the combined remainder of thymine (T). Repair recovery is deactivated permanently during transfer of the alkyl group of the protein, removing what alkyl group, each protein involves the use of a sacrificial protein directly. Some Methyltransferasea Examples of enzymes involved in direct reversal repair. MGMT is an important enzyme used in a direct reversal of O6-alkyl guanine DNA damage in our body. This is a common protein that up to the eukaryotes from prokaryotes, found in all living organisms.

Direct recovery of DNA damage repair is a mechanism that is used to restore the damaged DNA. This is the method most energy efficient, but some kind of damaged DNA is repaired in this way. Replication or transcription of past sites received the formation of the main types of damage pyrimidine dimer, by ultraviolet radiation, damage to the block and double helix distortion. Causing a direct conversion dimerization reaction, the process photoreactivation recovers the initial pyrimidine bases by it. O6 is done in mammalian cells direct reversal of protein O6 adduct caused by chemotherapeutic agents – methylguanine DNA methyltransferase (MGMT). Some tumors resistance to alkylating agent therapy MGMT and overexpression.

Direct inversion of damages, there is a case to be able to see would be the easiest way to fix the damage, but not thermodynamic reasons exercise is the reverse reaction in the case of most of it. In some cases, the reaction is reversible, in some of such cases, the mechanism has been developed to take advantage of the reversibility. Research CPD enzymes best these are photoreversal of CPD photolyase. Called “photoreactivation” is catalyzed by CPD photolyase, the reaction is found, there is a first process of DNA repair. It, long before that was discovered in 1953, the double helix structure of DNA was discovered by phage genetics in 1949.

CPD photolyase, contains two chromophores responsible for the absorption of solar energy. In photolyases of all these, FADH, and or some other methenyl chromophore, – tetrahydro or (MTHF) 8 – hydroxy -5 – deazaf ​​lavin – is a (8 HDF). (The yellow in the figure) transfer FADH-their energy (green in the figure below) the primary collector of light as 8-HDF act and MTHF. Then FADH energy is used to separate the dimer. Not the discovery bacteria, fungi, plants, in many vertebrates, CPD photolyases is a mammalian placenta. Insects, reptiles, not amphibians, (who repair 6 4PPs) ,6-4 photolyases are, and have been found E. coli, mammalian or yeast also is.

Interestingly, if you want to download, and the correction is genetic engineering mouse to the sensitivity of the skin to UV damage to express photolyase of foreign genes CPD significantly. 6-4 photolyase gene abroad are less effective. These results, I show that the production of CPD is more serious, in the case of mouse 6-4 photoproducts problem.

Another example of direct damage repair is the repair of O6-alkylguanine by transferring an alkyl group of cysteine ​​of the protein from the DNA, the O6-alkylguanine-DNA alkyltransferase. It is an alkyl group of working with this protein in size from methyl benzyl. Homologues of this protein is present in all organisms. Unfortunately, when the alkyl group is transferred to a protein, the protein, (alkyl cysteine ​​is a very stable) is deactivated permanently. The additional repair, it requires the synthesis of new protein molecules. In other organisms, alkylated versions of proteins that induce increased transcription of genes encoding proteins that achieve this and possibly E. coli. Epigenetic silencing of the human gene encoding this protein leads to increased mutation frequency, I increased the susceptibility to cancer.

AlkB, the most third example of direct damage repair is provided by proteins found in (including human) organisms probably all. Using the oxo intermediate, α-ketoglutarate – iron – For oxidation of the active compound this protein, an enzyme known as ((II) oxygenase AKG-iron) dependent oxygenase – iron-dependent It is a member of the class. In the process, α-ketoglutarate is converted to CO2, such as any of the steps of the tricarboxylic acid cycle and succinic acid.

Because DNA is a repository of genetic information of living cells of all, the stability and integrity are essential to life. The DNA, however, is not inert, and damage targeting undergraduate attack from the environment, resulting, if it is not repaired, it leads to diseases and possibly mutation. Form of sunlight (in the example perhaps the best known of the connection between the cancer, disease and DNA damage, skin induced by the environment that may be caused by exposure to a lesser extent UV and in, Sun) . Another example is the damage caused by tobacco smoke, which can lead to mutations in lung and subsequent pulmonary cells. May from the agent of the environment, DNA also, to receive metabolism, such as free radicals, by-products apart from oxidative damage. In fact, is that it is possible to make the individual suffer from a change in one million DNA per day.

In addition to gene damage caused by the environment of the process of replication of DNA during cell division, and error-prone. Percentage of the DNA polymerase adds nucleotides erroneous DNA replication at the time is a major factor in determining the spontaneous mutation rate in the body. “Correction” enzyme is generally recognized, while correct many of these errors, several mutations are, survive this process. It estimates the frequency of receiving the correct permanent human DNA errors in the range of 10-6 1 × 10-4 ~ 1 × mutant gametes per gene given. × 10-6 scientist size of 1 is that you will expect to find a mutation in a specific locus of 1 million gametes. Mutations in other organisms have much lower often.

One way can be used to assess the mutation, researchers take into account the speed of the new dominant mutations identified a variety of loci. For example, by examining the population number of individuals had been diagnosed with (disease caused NF1, the non-inherited dominant mutation or spontaneous) neurofibromatosis, researchers spontaneous mutation rate of the gene responsible for this disease is a mutation of 1 × 10-4 average of gametes per found. For example, mutations in other genes, such as that for the treatment of Huntington’s disease, other researchers have found that there was significantly lower than the cost of NF1. The fact that researchers have reported the mutation rate of different genes of another, the locus of some, it appears that failure or other error is more likely to occur.

Many of the proteins present in prokaryotes and eukaryotes, corresponding, DNA repair process is stored in a highly evolved. In fact, such damage, the cells evolved numerous mechanisms to detect and repair various types that might whether due to error or replication environment and impair DNA have. The DNA, since the molecule plays an active role in cell division, the control of DNA repair is associated with cell cycle regulation closely. The DNA cells and cell DNA replication (G1, S, cells. Remembered through the loop consisting of the DNA replication that occurs in mitosis and S phase G2, layer M, in M ​​phase) ensure During mechanism checkpoint cell cycle Before you can split occurs, it is as it is. Damage to these points, you can bring the accumulation of damage leading to mutations in order.

Affect various systems of the body, especially the predisposition of cancer, the number of genetic diseases of humans, defects in DNA repair to the base of the common functions of the constellation. These failures, (AT) ataxia telangiectasia has been included in denatured state engine due to a failure to repair oxidative damage to the cerebellum, xeroderma pigmentosum (XP), or poor sunlight I will repair the damage path state characterized sensitivity to ultraviolet light main relevant (UV). Further, RAD of such groups, the number of genes involved in cancer, the code is also defined an important protein for the repair of DNA damage.

Photoreactivation and NER is not the only way for DNA repair. For example, it is a major mechanism for handling DNA damage spontaneous reactions caused by other species that are generated by free radical metabolism (BER) base excision repair. With offices and operations, you may want to oxidation by reacting with these drugs, resulting in hydrolysis or alkylation. For example, the methyl group (CH 3) chemicals, often 7 – may alternatively be added, purine group be lost to form an methylguanine. All of these changes cause abnormal base that must be removed and replaced. Thus, enzymes known as DNA glycosylase, the bases and sugars that literally – to remove the base-damaged cutting the strand DNA by cleavage of the covalent bond between the phosphate backbone. Then, the polymerase repair fill gap obtained is sealed by ligase. Many of these enzymes are found in cells, each of which is a key specific to certain changes.

Another form of DNA damage is a double-strand breaks, gamma rays, such as X-rays, caused by ionizing radiation. These holidays are very harmful. In addition to preventing the transcription or replication, said portions could lead to chromosomal rearrangements and chromosome, which is attached to other chromosomes. Gene was disrupted in the process leading to inappropriate activation of the gene or fusion protein. Certain types of cancer is associated with such a conversion. Homologous recombination and repair (NHEJ) non-homologous end joining (HRR): double-strand breaks are repaired using either of two mechanisms. In NHEJ, an enzyme called DNA ligase IV using the overhanging portion of the DNA adjacent to the break in order to participate in all fill. If the preparation for the cell is completely isolated, the DNA is not replicated, if there are more errors, it can be introduced during the process. In contrast, the HRR during the homologous chromosomes, and is used as a template for repair.

Mutations in the DNA of the body is part of life. Genetic code we have been exposed to insult the various threatening its integrity. However, strict system of checks and balances, is in place by the DNA repair mechanism. Slip associated with the disease sometimes but errors that They are also a source of changes that are achieved by a long-term process as natural selection and evolution.