DNA Repair Systems and Cancer Therapy

DNA lesions leading to cell cycle arrest and thus allowing repair. if the damage is too heavy,it can induct apoptose in cells. Ionising radiation (IR) and most chemotherapeutic agentscurrently used in the treatment of cancer can damage DNA directly and indirectly. Soresistance to DNA-damaging agents can be related to increased cellular repair activitiestherefor defects in DNA repair pathways result in hypersensitivity to these agents. Cells ableto detect and repair the many different lesions caused by chemical and physical DNAdamaging agents with DNA repair machineries. Double strand breaks (DSBs) are the mostlethal of all DNA lesions. DSBs can cause chromosomal rearrangement and aneuploidy.DSBs can be induced by IR, free radicals and many anticancer. The HR and The NHEJrepair the DSBs during the cell cycle. DNA repair systems is to protect living organisms fromthe mutagenic and toxic lesions caused by DNA-damaging agents. two kinases of thephosphatidylinositol 3-kinase (PI3K) super-family, ataxia-teleangectasia mutated (ATM) andATM-RAD3-related (ATR), have key role in sensing DSBs . they can activate transductionpathways so leading to cell cycle arrest and facilitation of the repair process. it isunderstandable that any strategy aimed at inhibiting DNA repair enzymes is inherentlyassociated with a high degree of risk to produce damage to normal tissues. With theimplementation of microarray and proteomic technologies, the molecular characterisation ofhuman tumours has been cumulating in the past years. This information, together with boththe mechanisms of action of the anticancer agents and the pathways involved in the repair ofthe lesions they cause, can be useful for treatment of cancer, with a potential increase of thetherapeutic index. DNA damaging agents seems to be one of the few realistic ways toachieve tumour regressions in an effective way. Nevertheless, research on cell response toDNA damage and DNA repair is a useful way for new therapies based on the combination ofDNA damaging agents with DNA repair inhibitors.

کلیدواژه ها:

Ionising Radiation (IR) ، Homologous Recombination (HR) ، Double Strand Breaks ، Ataxia-Teleangectasia Mutated ، ATM-RAD3-Related (ATR)