DNA glycosylases

DNA glycosylase are a family of enzymes involved in the classification 3.2.2 base excision repair EC number, EC. Base excision repair is a mechanism that in order to remove the base which the damaged DNA is them replaced. DNA glycosylase catalyzes the first step of this process. To leave as it is created, the sugar phosphate backbone, the apyrimidinic / apurinic site is known as an AP of place, they remove the nitrogen bases damaged. Is achieved by inverting the damaged bases of a double helix, which cleaved the N-glycosidic bond. It was discovered bacteria is found in the first glycosylase, in the kingdom of all of later life. In addition to their role in DNA glycosylase of base excision repair enzymes, and other plants tabacum of demethylation active who were involved in the suppression of gene silencing Arabidopsis A., in N.. 5 – to access the chromatin structure of proteins and enzymes required subsequent transcription and translation, cut methylated cytosine, methylcytosine residues are substituted.

DNA glycosylases

DNA glycosylases has  two classes of mainly the glycosylase: bifunctional and monofunctional. Without the need for AP endonuclease In addition bifunctional glycosylase, creates a strand scission, while having AP lyase activity can reduce the phosphodiester bond of the DNA, monofunctional glycosylase, a sole glycosylase activity they have. The site of the AP lyase glycosylase β-elimination, can be obtained β-unsaturated aldehyde ‘, phosphoric acid product different AP endonuclease cleavage, in the vicinity of 3 ‘5 α. Some glycosylase – lyase 3 ‘3 further – can be run in a phosphate “turning the aldehyde the δ-elimination.

Crystal structure of the first DNA glycosylase was prepared in E. coli second. This structure revealed that the turning base damaged from the double helix at the active site pocket for the enzyme obligations. Other glycosylase been found to follow the same general paradigm, including the following human UNG image later. The cleavage of N-glycosidic bond, monofunctional glycosylase is using one molecule activated carbon water to attack the substrate. Instead, using the amine residue as a nucleophile to attack the same carbon, functional glycosylase, through the Schiff base intermediate.

In molecular biology, uracil DNA glycosylase (UDG), a family of proteins, an enzyme that returns a mutation in DNA. Common mutations most deamination of cytosine to uracil. UDG will repair these mutations. UDG is important for DNA repair, but these mutations do not can cause cancer. DNA glycosylase a T / U mismatch-specific single-stranded selective monofunctional uracil DNA glycosylase and (Mug) (SMUG1: This location DNA glycosylase and associated DNA glycosylase of uracil different uracil DNA glycosylase and (EC), febrile uracil DNA represents glycosylase, the G). By spontaneous deamination of cytosine, DNA is, remove the uracil glycosylase uracil from DNA may or caused by any of the incorporation of Miss Du against DA in DNA replication at the time. Prototype member of this family is the Escherichia coli UDG, which is one of the glycosylase found in first. Have been identified in mammalian cells, including MBD4 and, SMUG1, TDG UNG uracil DNA glycosylase activity four different. They, subcellular localization and substrate specificity is different. In addition, single-stranded DNA is preferably as SMUG1 board, I removed the U of double-stranded DNA.

In addition to the unmodified uracil, SMUG1 consumption tax 5 hydroxyuracil, 5 – can be 5 formyluracil bearing that oxidation of the group ring and C5 hydroxymethyluracil. MBD4 and TDG is a specific strictly for double-stranded DNA. Derivative of U and carbon 5 presented for TDG remove thymine glycol, of guanine, has been modified. The data, in human cells, the SMUG1 and TDG, indicates that it is an enzyme the main responsible for the repair of U: uracil caused to DNA by G miss DOO uptake whereas deals with UNG primarily mispairs caused by cytosine deamination spontaneous. I is considered MBD4 be correct T: G mismatches arising from deamination of methyl cytosine – thymine, 5 CpG sites. The MBD4 mutant mice do not show reduced pressure or survival increased cancer susceptibility not develop properly. However, they obtain a plurality of mutations at CpG sequences of the CT in the small intestine epithelial cells. Structure of the human UNG as a glycosylase other, it was apparent to switch to a base target of the double helix at the active site pocket, that complexes with DNA. UDG undergoes a conformational change from the closed” that is not””” open link in a state bound to DNA.

Usually, various glycosylases has evolved to recognize the base is oxidized formed by reactive oxygen species generated during metabolism of the cells. Lesions most commonly formed on guanine residues, 2,6 – a oxoguanine – diamino – 4 – hydroxy – 5 – 8 formamide (FapyG). The G to T transversion, as a result, ,8-oxoG is mutagenic highly because of the pairing and wrong adenine during replication. HOGG1 the helix hairpin repair of this lesion is initiated by a pair recognize functional DNA glycosylase OGG1, and 8 oxoG C. – is a bifunctional glycosylase belonging to the helix (IUU) family. If you want to recognize the adenine, I found that mispaired consumption tax but ,8-oxoG left as 8 oxoG. The OGG1 knockout mice, which showed an increase in the incidence of tumors, as they age, did not accumulate 8-oxoG in the liver. Invalidation is found at the same time as was observed in the loss of phenotype found similar to [23], then why OGG1 8-oxoG accumulation in various tissues, including the small intestine and lung in case. [24], mutant has been found that if they are associated with an increased risk of colon cancer and colon polyps in humans. In addition to OGG1, when NEIL3 DNA glycosylase three additional and NEIL1, NEIL2 is included, human cells were found to be. These are homologous to Ney of bacteria, there may explain why mild phenotype OGG1, it was found that if the knock-out mice present.