Proteins involved in BER have been introduced in clinical practice due to the increase in our understanding of the pathways involved in signaling targeted therapies for cancer and cell proliferation. Targets and emerging new a protein involved in DNA repair pathways. For example, inhibition of various proteins in the DNA repair pathway, increases the sensitivity of cancer cells to DNA damaging agents such as radiation therapy and / or chemotherapy. We Investigate the factor -1 1/redox apurinic endonuclease, redox signaling run target for superior sensitivity of tumor cells to chemotherapy or believe a decisive role in the redox and DNA repair I and. Ape1/Ref-1 is a key enzyme in (BER) base excision repair pathway is responsible for the repair of DNA damage caused by alkylation and oxidation. The Ape1/Ref-1 is, more importantly, to maintain the transcription factor in the active state of decline as a function of redox agent. As people of other AP-1, resulting such, HIF-1α, and, of, p53 CREB, Ape1/Ref-1 the DNA binding activity of multiple transcription factors that are involved in promoting the development of cancer to promote. To discuss what is known as about the pharmacological activity of the target DNA repair, we will investigate the Ape1/Ref-1 promising clinical benefit from inhibition of one of these features in the treatment of cancer and redox activity. A brief description of the effect of polymorphism in the DNA sequence, it can be included in importance for Ape1/Ref-1 for the maintenance and integrity of the genome. Experimental change of Ape1/Ref-1 response of biological cells to change and DNA-damaging agent of activity, suggesting that Ape1/Ref-1 is also an object productive of chemoprevention. In this review, we examined the activity Ape1/Ref-1 reader, as well as the potential of the protein, to explore its role in chemoprevention as targets in cancer therapy.
Proteins involved in Base excision repair (BER) in charge to prevent interruption thousands, of a continuous chain of DNA repair lesions thus caused premature aging, cancer, by endogenous human disease and many other, to maintain the integrity of the genome The repair of the line the first system, it has not been, mutation of exogenous. In addition to tight control of the continuous availability of the essential ingredient, not only required for the repair quickly and accurately, a mandatory feature prevents replication of damaged DNA and this basic and BER In order to, requiring spatial and temporal adjustment of cell cycle progression and BER. The main purpose of this review is to examine the new problems and controversy mammals meet the BER of links to DNA replication and DNA damage checkpoint road BER mechanism to regulate the BER capacity critically.
Arise due chemical changes in other hydrolyzed DNA base oxidation bases, and non-enzymatic methylation is lost, the chemical instability of specific DNA molecules in cell culture medium, exogenous by DNA or lesions (Environment the effect of multiple endogenous) and (intracellular) DNA reactive species. Result of interference with cell metabolism and accumulation of mutations, such modifications of the DNA is corrected if it is possible to react with replication and transcription of DNA. Among the many strategies, base excision repair (BER) pathway is a major repair to fix some changes to DNA found in DNA generally to maintain the reproduction and normal function of DNA project. BER deficiency affect genomic stability, and are involved in human diseases including many cancers premature aging, and neurodegenerative diseases. The human cells, respectively, which is believed to be 10000-20000 DNA damage repair daily. The enzymes involved in BER, catalyzes the excision of nucleotides to recognize the DNA bases damaged, damaged, please replace damaged, with a new one. Most of the BER is carried out by bringing the removal and replacement of one base and the so-called short patch BER. Nucleotide excision time BER so leads to transient formation of single strand breaks BER enzymes DNA, of course, is an important player in the repair of SSB. BER reaction in the cells is very fast, in many cases, it is possible to take a few minutes to the BER of individual events. Repair of DNA damage and require several rounds of BER rapidly, it may take several hours depending on the size of the BER enzymes are limited.
There is no convincing evidence for the regulation of the cell cycle of BER, but it is assumed on the basis of biochemical properties of BER enzyme, the majority of the preferred double-stranded DNA substrate, the BER is to act primarily through the G1 phase The cell cycle is reasonable. G1 in BER activity is prepared for DNA replication by maintaining the transfer error-free, to remove DNA damage. If the DNA base damage is not removed before the start of the replication of DNA, the integrity of the genome DNA synthesis overcome referred containing special POLS capable of performing an error-free DNA synthesis in a wide range of DNA damage, base provided by the backup system. TLS POLS, seven of them, human cells have 15 POLS 11 which can function in the BER has been proposed. Primary enzyme BER nuclear DNA Pol · β, Pol γ while involved in the BER of mitochondrial DNA. In addition, POLS is described AP lyase activity suggests feature in θBER and λ, have been identified in the POLS and long patch BER and δ is ε ι is included. Indeed, Pol λ is participating in allocation MUTYH / Pol λBER the road. 11 POLS and 7 POLS BER support combinations of potential functions to the fact that may be employed to maintain and repair a precise and efficient DNA base damage and perform backups reliable TLS ensures the BER. They, This conclusion, accumulated base damage of the DNA of non-repair, and survival (except thymine-DNA glycosylase) knockout mouse DNA glycosylase of all during the lifetime of you have suggested “correction” function are supported by the TLS strongly BER which is supported by the observation that it is fertile. However, ultra-small base station apparatus of unrepaired BER generated, the (DSB) DNA double-strand breaks that require (HR) repair homologous recombination or (NHEJ) joint end non-homologous either to be hit the fork of the DNA It has the potential to. Question, HR and NHEJ or can provide a method for maintaining genome stability backup repair capacity? Since not much Perhaps the XRCC1 and DNA ligase IIIα related to the repair of ultra-small base station equipment, all attempts to generate Pol β-deficient mice, led to early embryonic lethality. Haploinsufficiency to repair (inactivation of alleles of one gene), an ultra-small base even with the results of POLβ genetic susceptibility to DNA damage and significant genomic instability, which means that the BER is a key cellular system is responsible for