title: Redox modulation of the DNA damage response.
abstract: Lesions to DNA trigger the DNA-damage response (DDR), a complex, multi-branched cell-intrinsic process targeted to DNA repair, or elimination of the damaged cells by apoptosis. DDR aims at reducing permanence of mutated cells, decreasing the risk of tumor development: the more stringent the response, the lower the likelihood that sub-lethally damaged, unrepaired cells survive and proliferate. Accordingly, leakage often occurs in tumor cells with compromised DDR, accumulating mutations and accelerating tumor progression. Oxidations mediate DNA damage upon different insults such as UV, X and γ radiation, pollutants, poisons, or endogenous disequilibria, producing different types of lesions that trigger DDR, which can be alleviated by antioxidants. But reactive oxygen species (ROS), and the enzymes involved in their production or scavenging, also participate in DDR signaling, modulating the activity of key enzymes, and regulating the stringency of DDR. Accordingly, antioxidant enzymes such as superoxide dismutase play intimate and complex roles in tumor development, exceeding the basal roles of preventing the initial DNA damage. Likewise, it is emerging that dietary antioxidants help controlling tumor onset and progression by preventing DNA damage and by acting on cell cycle checkpoints, opening a novel and promising frontier to anticancer therapy.
authors: Dipartimento di Scienze e Tecnologie Chimiche, Universita' di Roma Tor Vergata, Roma, Italy.
authors: Fanny
authors: F
authors: Caputo
authors: Rolando
authors: R
authors: Vegliante
authors: Lina
authors: L
authors: Ghibelli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001688:Biological Products / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D004260:DNA Repair; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D008938:Mitosis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001688:Biological Products; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase