title: Spontaneous DNA repair in human mononuclear cells is calcium-dependent.
abstract: Spontaneous DNA repair in peripheral blood mononuclear cells (PBMC) has been recently described. The aim of this study was to evaluate whether spontaneous DNA repair is Ca(2+)-dependent, as in vitro-stimulated DNA repair. Spontaneous DNA repair in PBMC was measured in a 1mM Ca2+ medium. The effect of extracellular Ca2+ chelation by EGTA, intracellular Ca2+ chelation by bapta-AM, and Ca2+ loading by the ionophore A23187 was examined. The signal transduction pathway was evaluated by inhibiting protein tyrosine kinase with genistein, calmodulin with W7, and calcineurin with cyclosporin A and tacrolimus. Extracellular Ca2+ chelation had no effect on spontaneous DNA repair, while both intracellular chelation and calcium overloading inhibited the DNA repair. Inhibition of protein tyrosine kinase, calmodulin or calcineurin reduced DNA repair. In conclusion, spontaneous DNA repair is mainly Ca(2+)-dependent at a narrow range of intracellular Ca2+ concentrations. The signal transduction cascade includes protein tyrosine kinase, calmodulin, and calcineurin.
authors.affiliation: Department of Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Ori
authors.forename: Michal
authors.initials: M
authors.lastname: Herman
authors.forename: Avry
authors.initials: A
authors.lastname: Chagnac
authors.forename: Tsipora
authors.initials: T
authors.lastname: Malachi
authors.forename: Uzi
authors.initials: U
authors.lastname: Gafter
authors.forename: Asher
authors.initials: A
authors.lastname: Korzets
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D004260:DNA Repair; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D065095:Calcineurin Inhibitors; D002147:Calmodulin; D002614:Chelating Agents; D007476:Ionophores; D000001:Calcimycin; D011505:Protein-Tyrosine Kinases; D002118:Calcium