Impaired synthesis of heme oxygenase-1 in Fanconi anemia cells can be rescued by transfection of Fanconi wild-type cDNA.
Fanconi anemia is a fatal, hereditary chromosome instability syndrome of early childhood with progressive pancytopenia and cancer-proneness. Hypersensitivity to alkylating agents points to DNA repair inefficiency. Excess reactive oxygen intermediates and hypersensitivity to oxygen, all features of Fanconi anemia cells, give evidence for a disturbed oxidative metabolism. Here, we report that expression of the inducible heme oxygenase-1, an essential antioxidative defense protein, is impaired in Fanconi anemia cells and can be reinstated with the transfection of Fanconi A wild-type cDNA. A causative interaction of Fanconi anemia proteins with transcription of selected proteins is indicated. The results enlighten the oxygen sensitivity in Fanconi anemia.
Kontou
Maria
M
Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin, Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195, Berlin, Germany.
Hirsch-Kauffmann
Monica
M
Schweiger
Manfred
M
D002460:Cell Line; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005199:Fanconi Anemia / Q000201:enzymology* / Q000235:genetics; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins; D014162:Transfection
D018076:DNA, Complementary; D052217:Fanconi Anemia Complementation Group A Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C494631:VAC14 protein, human; D051547:Heme Oxygenase-1