title: Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation-treated cockayne syndrome B cells.
abstract: We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)-induced pH2AX foci, an indicator of DNA double-strand breaks, is significantly delayed in IR-treated cells belonging to the B complementation group of cs (csb). Using alkaline single-cell gel electrophoresis, which predominantly detects single-strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild-type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome.
authors: Laboratory of Molecular Mutagenesis and DNA Repair, Department of Epidemiology, Prevention and Special Functions, Istituto Nazionale Ricerca Cancro, Genova, Italy.
authors: Monica
authors: M
authors: Ropolo
authors: Enrico
authors: E
authors: Cappelli
authors: Mara
authors: M
authors: Foresta
authors: Alessandro
authors: A
authors: Poggi
authors: Luca
authors: L
authors: Proietti-De-Santis
authors: Guido
authors: G
authors: Frosina
mesh_terms: D002460:Cell Line; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000378:metabolism* / Q000473:pathology; D053960:DNA Breaks / Q000528:radiation effects*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D019085:Fluorescent Antibody Technique, Direct; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: C468783:H2AX protein, human; D006657:Histones; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes