DNA Repair, Cancer and Cancer Therapy - The Current State of Art

DNA Repair Based Therapy in Oncology and Neurodegeneration

“…It has been shown that DNA damage is a usual event which is also underlying cause of many disorders such as cancer and other inherited or acquired pathologies. There are many endogenous and exogenous sources which cause DNA damages interfering with genome [1].…”

“…Depending on the phase of the cell cycle, there are two major intracellular DNA DSB repair pathways: homologous recombination (HR) or non-homologous-end joining (NHEJ) [1,20]. As chromosomes are duplicated during S-phase of the cell cycle, double strand breaks (DSBs) during S/G 2 can be repaired without any loss of information, by recombination between the damaged and its homologous undamaged counterpart.…”

“…Homologous recombination uses a sister chromatid in S and G 2 phases as a template; NHEJ is an error-prone method of directly ligating the DSB ends in G 0 and G 1 phases. HR involves BRCA1, BRCA2 and Rad51 proteins and NHEJ involves Ku70/80, the DNA-PK, and DNA ligase IV [1]. During migration and differentiation, there is dependence on NHEJ pathways, so mutations in the NHEJ pathway can result in loss of neuroprogenitor cells, cortical neurons and finally results in microcephaly.…”

“…SSBs are usually repaired by the SSBR and NER pathways. Nucleotide-excision repair (NER) is mainly responsible for repairing pyrimidine dimers having important roles during G 1 phase to remove bulky lesions, caused for example by ultraviolet irradiation [1]. But if those pathways are defective, they can trigger apoptosis by blocking the progression of RNA polymerases [26].…”

“…DNA damaging genotoxic therapeutics can be divided into groups due to their mechanism of action and type of damage induced. Alkylating agents and platinum-based agents directly effect DNA to induce bulky DNA damage and those are repaired by the nucleotide excision repair pathway (NER) [1,31,32]. Direct methylating agents cause damages that are repaired mainly via the base excision repair pathway (BER) [31].…”