Involvement of the Fanconi anemia protein FA-C in repair processes of oxidative DNA damages

Fanconi anemia (FA) is an autosomal recessive disorder characterized by ske letal abnormalities, pancytopenia and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hypersensitivity towards oxygen and cross-linking agents such as diepoxybutane and mitomycin C. An increase d level of reactive oxygen intermediates and an elevation of 8-oxoguanine i n FA cells point to a defective oxygen metabolism in FA cells. We investiga ted the repair activity of oxidatively damaged DNA in lymphoblastoid cells from FA patients of complementation groups A-E. The repair activity for oxi datively damaged DNA was significantly reduced in lymphoblastoid cell lines of complementation groups B-E, Complementation of the FA-C cell line with the wild type FA-C gene restored the repair activity to normal, This indica tes that the FA-C protein participates in the repair of oxidatively damaged DNA. (C) 1998 Federation of European Biochemical Societies.