There is a change in DNA sequence (expressed SNP, a slice, scissors s) single nucleotide polymorphisms to one base generator -, G T, or C, – pairs or members of the species (shared sequence or other) genome It is a different human chromosomes between. For example, two order DNA fragment includes AAGCCTA of AAGCTTA, the difference of a single nucleotide from different individuals. In this case, I say that the two alleles are present. SNP general all have alleles only almost 2. Genomic distribution nonuniformity of the SNP, the SNP, or occurs in non-coding regions than code area more frequently than usual, in general, act as natural selection, and the allele SNP most advantageous genetic adaptation lock. Other factors, such as mutation rate and gene recombination such is able to determine the concentration of SNP.  Strong predictor of microsatellite AT density SNP is in the region of low GC and density SNP paths long (AT) of (o) is greatly reduced, especially: that is provided by the presence of microsatellite SNP density I will not take into account the trend found.

In the population, can be assigned to less frequent allele SNP is – sites that are observed in groups that were given, the allele frequency of the lowest. This is a low allele frequency of two for the single nucleotide polymorphisms only. Because there is a difference between the human population, SNP allele that is common in ethnic groups and one geography, may be rare much different. Genetic variation of these between individuals, is performed DNA assay, above which (especially in non-coding part of the genome) was used in forensics. In addition, the genetic variation of these, underlying the differences in the sensitivity of our disease. The severity of the disease, the method also body responds to the treatment, which is a manifestation of genetic mutation. For example, mutations have been associated with an increased risk of Alzheimer’s disease in Besuapo (apolipoprotein E) gene.

transcriptional Important genes of two of U~eineru that shows the effect of phenotype and function of polymorphism is a gene XPC and XPD. Further, in addition to the activity of other, XPD, also known as ERCC2 serves the detection of DNA surrounding the lesion site during the NER. The study, are associated with a genetic predisposition to several types of cancer (A> T) is (Lys751Gln) exon 23 (G> A) and (Asp312Asn) polymorphism in exon 10 have shown that . Responsibility XPC gene of the protein that recognizes the DNA between the early part of Pasuabuneru. This gene, may have a polymorphism in exon 15 of the SNP that is associated with the risk of cancer as well as intron 9. The study, that skin cancer, breast cancer, polymorphism insertion / deletion allele, poly (AT) XPC intron 9 is associated with an increased risk of prostate cancer in a population of northern India in particular has been shown.

Hereditary cancer, research of xeroderma pigmentosum have identified several genes that encode proteins in NER path are two of them there XPD and XPC. It is caused by a homozygous deficiency of (TC-NER) repair of UV DNA damage that increases the risk of skin cancer patients, more than 1000 times XP. In heterozygous patients, the risk of cancer is sporadic, but may be provided on the basis of the analytical evaluation of the genetic polymorphism associated with DNA repair XP from purified lymphocytes. After the recurrence rate of research and III colon cancer, XPD (ERCC2) polymorphism 2251A> C was correlated with chemotherapy after early recurrence significantly stage II and high-risk. The effect of channel gene polymorphism, studies have shown that it is an additive the presence of cancer have a higher frequency of mutants in the risk significantly.

(Sometimes known as UvrD in this complex) DNA helicase II UvrA, UvrB, and UvrC: UVR UvrABC endonuclease enzyme complex consisting of four proteins, E. coli repair processes remove nucleotides, (E. and is controlled by coli). First, UvrA-UvrB complex scans the DNA of recognition and UvrA subunit of failure in the spiral caused by such as pyrimidine dimers. When you recognize the subunit of such distortion, binds to UvrB monomer and UvrC protein that comes leaves and complex UvrA, therefore, represents a new UvrBC dimmer. 4 nucleotide phosphodiester bond downstream UvrB cut of 8 nucleotide phosphodiester bond UvrC cut DNA damage and a 12 nucleotide segment creation and cut DNA damage upstream. Remove the cut segment to come in then, DNA helicase II is, break the hydrogen bonds between complementary bases aggressively. Then difference obtained is filled in using a DNA ligase and DNA polymerase I. Primary resection process is very similar to the higher cells, which typically includes a protein far more these cells – E. coli, is a simple example.

Is present in bacteria, TC-NER is carried by the TRCF (multi) protein. Using ATP hydrolysis to move the double-stranded DNA upstream of the transcription bubble, TRCF is SF2 ATP ase move is the RNA polymerase is the dissociation of the first of the three-way extension of the forward RNA polymerase complex. Earn ultraviolet (A) BC nucleotide excision repair machine by direct physical interaction with UvrA subunit also TRCF

Two UvrA protein to form a dimer, and has an ATP-ase / GTP-ase activity of both. Damage.The UvrA dimmer bind to dimeric UvrA, and to DNA can be by a mechanism for detecting the violation of double helix DNA, and operates detected as means for detecting DNA damage probably I will form a trimmer UvrB. UvrB part of the trimmer gives the double helix of damage. Binds to UvrB monomer and UvrC proteins that come with leaves of UvrA dimer, therefore, represents a new dimmer UvrBC. This dimer is responsible for the cutting of nucleotide on each side of the DNA damage. 12 nucleotide segment excision and creating DNA damage of 8 nucleotides upstream phosphodiester bond UvrC cut and downstream of nucleotide DNA damage of one phosphodiester bond 4 UvrB cutting. (It is sometimes called UvrD), then, by removing the base pairs, DNA helicase II, has an ablation Delete segment. Torn at this point UvrC it is possible to participate in order to prevent re-annealing UvrB, the cut DNA but is UvrB will remain in force. DNA polymerase I is filled, it comes in the correct order nucleotide UvrB relay processing, the latter is complementary phosphodiester bonds by DNA ligase.
Pyrimidine dimers was molecular lesions formed from thymine or cytosine bases in DNA by photochemical reaction. UV causes the formation of covalent bonds by localized reaction to the double bond C = C. In the form of dsRNA, uracil dimer may be accumulated as a result of ultraviolet radiation. UV general product one is, (, CPD is containing the thymine dimer) cyclobutane pyrimidine dimers and are 6,4 light generation. to change the structure of DNA, these lesions are premutagenic, replication arrest and inhibition polymerase. I can repair, dimer is unrepaired dimers mutagenicity by the nucleotide excision repair or light recovery. Pyrimidine dimers are the main cause of melanoma in humans.

Pyrimidine dimers will introduce the local structural changes in the DNA structure that allows recognition of a lesion of repair enzymes. You can be repaired by photoreactivation in most organisms. Photoreactivation is a repair process that photolyase enzyme to reverse the CPD is by direct photochemical reaction. Following absorption (i.e., sunlight or fluorescent light) of the wavelength of light> of 300 nm, DNA strand lesions are recognized by these enzymes. It enables the absorption of the photochemical reaction that occurs leading to removal of the dimer pyrimidine, it is returned to the original condition.

Nucleotide excision repair is a general mechanism for the repair of the lesion. Were excised the CPD, this process, the synthesis of new DNA instead of the surrounding area of ​​the molecule. Leading to some of the tumors exposed to UV light and skin discoloration are missing, xeroderma pigmentosum, nucleotide excision repair process is a genetic disease in humans. Pyrimidine dimers of unrepaired in humans, can lead to melanoma.

Global genome NER repair damage to the non-transcribed DNA strand and transcription of the gene of active and inactive of the entire genome. – This process is not dependent on transcription. And allow the spiral failure and scan XPC-Rad23B complex genome continuously DNA damage binding of XPC-Rad23B complex with (DDB), using some “damage observation” protein, DDB1 this time The (XPE is responsible violates confirmed) DDB2, it is possible to recognize a particular type of damage by UV light and. In addition, XPA acts as a damage recognition is insufficient defined yet. To identify the site of damaged mobilize damaged DNA to confirm the presence of DNA damage then, DNA was subjected to excise duty damage lesions surrounding the repair patch then repair proteins following fill.

At any time, the majority of the genome in vivo, but not in the course of the transfer, but the performance difference between the transcriptional activation region and transcriptionally channel of the genome. For many types of disabilities, and repair of NER of transcribed strand of transcriptionally active genes more rapidly than DNA repair transcription silent and non-transcribed strand. GGR and TC-NER is different only in the initial stage of detection of DNA damage. The TC-NER, main differences GG-NER and TC-NER is that it requires the DDB strain or recognition XPC protein in mammalian cells. Stalls of RNA polymerase in lesions of the DNA when you start the TC-NER instead: RNA polymerase blocked, which acts as a fault signal recognition, to replace the need for recognition properties of the distortion of the DDB complex with XPC-RAD23B. Not damage DNA, CSB and CSA CS protein associates the type of XPC-Rad23B specific. Repair other mechanisms are possible, efficient and very accurate.

Is an important enzyme (TFIIH) is involved in the double resection transcription factor II H. The XPG and TFIIH, (XPG to stabilize the TFIIH) is recruited to sites of DNA damage first. They help to generate the junction between single-stranded DNA and double-stranded around the transcription bubble and relaxing the DNA – the XPD each TFIIH subunit XPB, to function as ATP ATPase and helicase You. In addition to the stabilization of TFIIH, while it decreases the damage to the DNA of the side “of the three having endonuclease activity, XPG is hetero XPF-ERCC1 protein 5 ‘end at 25 to 30 nucleotides difference circuit Double incision results in the removal of. single-stranded DNA cut dimer.  Replication protein is a protein of the last two related to the repair of NER complex and XPA main (RPA). Before you bind TFIIH as engaged in the verification of DNA damage, these two proteins are present they. They also, it is possible to protect the single-stranded DNA. Verification, after the side of 5 ‘side incision is made in three before, DNA repair is’ a. It helps to reduce the single-stranded DNA that is exposed during the repair process.

(Also called Neil Dingwall syndrome or Weber-Cockayne syndrome,) fault growth, development of the failure of the nervous system, Cockayne syndrome, rare always an abnormal sensitivity, and is characterized by premature aging sunlight (photosensitive) It is a congenital disorder of chromosome recessive. I heard an abnormal loss and other common and (pigmentary retinopathy) eye, but the problem of some or all of the internal organs can be considered. In addition, I related to the group of diseases called white matter atrophy. Basic conditions, a defect in DNA repair mechanisms. It is named after the English doctor Frederick Parkes Weber and physician Edward Alfred Cockayne of English. Neil Dingwall syndrome cause of Cockayne syndrome Neill.Mutations of Catherine A. and Dingwall of ERCC8 gene ERCC6 named Mary M. is attached. The transcription-coupled repair mechanism of DNA specific, proteins made by these genes are involved in the repair of damaged DNA in the active gene. If it is changed or ERCC6 ERCC8 gene, DNA damage is not adjusted. This damage because the accumulation, may lead to cell death or cell malfunction. Mutation of a gene mutation will make 70% of the cases ERCC6.

Nucleotide excision repair (NER), resection removal mechanism is particularly important mutations caused by UV-induced DNA damage. UV result in DNA damage in DNA adducts and bulky – these adducts, 6,4 and thymine dimer mainly – is light product. Recognition removal injury results in short single-stranded DNA segment lesions are included. It remains intact single-stranded DNA, DNA polymerase is used as a template for the synthesis of short complementary sequence. Forming ligation full Neil final, the double DNA, but is carried out by DNA ligase. I can NER is divided into 2 subpathways: link global genome transcription and NER NER (GG-NER) and (TC-NER). How to recognize DNA damage is different from both subpathways them, but they have the same method of ligation and repair of the lesion incision. The importance of NER has been evidenced by the severe human disease is the result of a genetic mutation that was born of the NER protein. Cockayne syndrome and xeroderma pigmentosum are two examples of diseases associated with Abner.

Since its inception, life, is facing a major problem that forms stored genetic information it is not chemically inert. DNA integrity is challenged impair its function, the harmful effects of physical factors and chemical plurality. In order to protect the Achilles tendon, a complex network of systems for DNA repair is done at the beginning of evolution. Versatile to counteract the deleterious effects of DNA damage including many basic types of induced damage nucleotide excision repair (NER), by environmental information source, one is the removal pathway of DNA damage that has been refined. The lesions most suitable under the panel, there are two main types of the victim that was generated by the short-wave UV light component product cyclobutane pyrimidine dimers and (CPD), of sunlight. Furthermore, chemical adducts bulky Many are removed by this process. Among the diverse spectrum of NER lesions, significant distortion of the helix of the DNA is common. Has been observed prototype repair syndrome xeroderma pigmentosum in (XP) the NER defect underlying the high sensitive predisposition to skin cancer. Represents repair genesXPA-G with different seven XP complementation group were identified.

Over the past decade, a major factor of all Neil has been cloned basis of the reaction of the “cut and paste” is dissolved in the in vitro from purified components. Recently, XPC has been identified as a repair factor recruitment to DNA damage sensor (complex with hHR23B). And a transcription factor TFIIH complex common with the separation of the intermediary chain and XPD helicase XPB, the lesion site. Check the damage found in the DNA structure, XPA is extremely important for the assembly of the rest of the repair mechanism. The (RPA), to stabilize the open DNA complex, ERCC1 and XPG, replication protein is involved in the positioning of responsibility XPF endonuclease incision of the DNA around the lesion. After removing the damaged containing oligonucleotide is 24-32 nucleotides, in order to close it, the length is a duplicate of the same factors fill the remaining gap in general.

Able to distinguish between two modes of channel you can: repair of damage on the genome all, because block transcription repair the lesions present in the DNA strand that has been transferred global genome NER and (GG-NER), transcription-coupled NER (TC called – NER). Defects of XP group harbor the most common component of both subpathways of NER. GG-NER is dependent on the activity of the factor of all of the above, including complex XPC-hHR23B of GG-NER-specific. Cost of repair of GG-NER for is highly dependent on the type of lesion. For example, the difference in affinity of the damage sensor XPC-hHR23B, perhaps, from the genome of CPD, 6 4PPs is removed much faster. In addition, the location of the lesion (access) can affect the removal rate in the in vivo. The TC-NER, damage is detected by extending the RNA polymerase II complex when it detects a lesion. Interestingly, significant failure, Cockayne syndrome is associated with a specific defect in transcription-coupled repair. Determination of (CS-B and CS-A) 2 complementation groups, indicating that it is particularly necessary for the repair quickly and efficiently strands gene product two is transferred at least.

Phenotype, CS tough and sensitive, it is a condition to be very versatile in terms characterized by premature aging and features of neuronal development,. Most of these symptoms, it is not seen even in NER-deficient XP patients in general. CS protein and transcription-coupled repair and / or show that you have a function outside the NER is further symptoms of CS. also that the binding of polymerase transcription elongation failure to block multiple pathways for repair, seems to be removed in transcription-coupled manner (such as oxidative damage, for example) non-NER lesions. Interestingly, the display function of the XP-G CS patients in combination with symptoms XP XP-B some, and XP-D,. However, people of XP-D and XP-C of the other suffer as CS-hair syndrome trichothiodystrophy brittle. This clinical challenge and point to the role of additional NER factors of these. The TTD mouse model is a mutation associated with XPD subdivision of the dual function complex TFIIH with basal transcription defects in the base of the TTD at least some of the events recently. Thus, associated with the heterogeneity of clinical surprisingly high for the additional features of the factors NER defects are involved Abner.