Direct reversal

Normally, the direct recovery used to repair the alkylation DNA, each was developed to repair damage to DNA comprising a particular extraneous enzyme a number of routes. Examples include cysteine ​​methyltransferase O O (6) – demethylation (6) methyl guanine – a methylguanine-DNA methyl transferase (MGMT). Enzyme O (6) – accepts the methyl group of the stoichiometry of methyl guanine nucleotide, it is inactivated in the process. MGMT, as suicide enzyme many enzymes involved in the recovery directly: you can each enzyme molecule catalyzes the reaction, then discarded. It is a costly process for the body, mutagenic and highly It is reserved for repair of DNA damage of cell toxicity. The presence of these enzymes indicate that exposure to alkylating agents regularly naturally occurring immediately DNA of biological evolution.

Direct reversal

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.