Irradiation effects in the treatment of cancer. 4.4. DNA Sch Ending signaling DNA Sch Ending is an object of the focus radiation in the cellular system. The first step is the damage caused by proteins Identify known as damage sensors. In the identification of the damage to the DNA ends are processed for repair and signals complexes can k Cellular To initiate re answers. There are a number of protein complexes capable of various types of DNA-Sch To be seen, however, the IR-induced Sch Ending comprising Haupts Chlich CBD is compared is the best characterized sensor of DNA-Sch the complex of the ATM. The first event after the induction of DSBs IR is the detection of the break and the Mre11 binding Rad50 Nbs1 complex, followed by the binding of ATM. The complex connects the two ends of the broken DNA repair further to erm Equalized. The delivery of the IR-induced rapid autophosphorylation on serine 1981 ATM protein comprising the Kinaseaktivit t responsible for the activation of effector kinases activated. Thus, a sequence of events seems to occur after DSBs: First, ATM is activated and set to the areas of Sch is caused by the MNR, on the other hand, mediation MRN DSB processing what follows to generate RPA-coated ssDNA, then what cause to do when setting ATR. The activation of ATM and ATR and triggers Irinotecan Topoisomerase inhibitor phosphorylation of downstream targets Chk1 and Chk2, respectively. Chk2 then phosphorylates Cdc25A phosphatase, five Hig dephosphorylation of Cdk2 entered Ing blockage of DNA synthesis and S-phase arrest The phosphorylation of Chk1 leads, the results of its translocation into the nucleus where they phosphorylate Cdc25A and thus to its degradation. The lack of results in Cdc25A phosphorylated CDK1 and CDK2 and to remain in their inactive states provoked Nd a arrest in G2 / M, the most important arrest observed in cells treated IR.
Subsequently, the repaired DNA strand breaks by two major common path in S Ugersystemen NHEJ and homologous recombination. HR uses essentially the other copy as a template for repair, but NHEJ Haupts Feeder chlich Llige connecting the beaches length with a group of proteins known as DNA-PK. The choice of track repair of the DSB is the stage of the cell cycle dependent Ngig that NHEJ is the dominant path in G0 and G1, HR, and dominated in S and G2 / M phase. The effectiveness of the IR is strong ability as a treatment by the F, The cellular effect To repair DNA re. Changes in protein levels of DNA repair have been Rocuronium correlated with resistance to strategies to control cancer. It is known that a mutation in one of the NHEJ proteins And the way in HR, so that the cells tend toradiation extremely sensitive to induced cell death. With this information, numerous studies have been conducted, targeting the machinery of DNA repair for sensitizing cells to radiation. These studies mainly on the proteins In NHEJ way to support especially DNA PK, which involve a DNA-dependent Independent kinase protein serine / threonine. DNA PKc the catalytic subunit of DNA-PK, and the second component is a Ku autoimmune antigen. On its own DNA PKcs is inactive, and relies on Ku-and heterodimers to direct the foreign DNA Its kinase activity sen t. All these components of NHEJ are overexpressed in many cancers and increased Hte expression is closely associated with me.