DNA Helix Destabilization by Alkylating Agents: From Covalent Bonding to DNA Repair

摘要: Preservation of the integrity DNA, carrier heritage information, is crucial for cell survival. Altered genetic information could lead to major perturbations in organization, function and proliferation cancer cells. Because cells are highly proliferative with high number replication, DNA was first clinically used anti-cancer therapeutic target drugs directly (intercalators/alkylating drugs) or indirectly (micro-tubules, topoisomerases inhibitors, modifiers histone acetylation...) targeting DNA. Despite actual development targeted chemotherapies (against membrane receptors, kinases, proteasome,...), direct still represent a part anticancer pharmacopeia terms total prescriptions efficacy. Compounds mainly bind three different ways: non-covalent (fitting minor grooves), intercalation between two successive base pairs, covalent bonding base, generally stabilization double helix. Only few from intercalating alkylating families destabilizes Cytotoxic effects agents (used/developed chemotherapy carcinogens) strongly attenuated by cellular repair processes. Optimal use therapy requires clear understanding their Similarly, knowing how cope carcinogensinduced damages interest regarding health our society, so prompt chemical compounds insufficiently studied long term toxicities sometimes eventually identified as carcinogens (food industries). processes infer both those Yin Yang aspects using machineries: excision (BER); nucleotide (NER: long/short-patch, transcriptioncoupled/global genome); mismatch (MMR); homologous recombination (HR) nonhomologous end-joining (NHEJ). Fanconi anemia (FA) acts coordinator pathways (Moldovan & D'Andrea, 2009). Since there yet various complete reviews on literature, present review will focus process destabilizing compounds.