Fanconi anaemia proteins: major roles in cell protection against oxidative damage.
Fanconi anaemia (FA) is a cancer-prone genetic disorder that is characterised by cytogenetic instability and redox abnormalities. Although rare subtypes of FA (B, D1 and D2) have been implicated in DNA repair through links with BRCA1 and BRCA2, such a role has yet to be demonstrated for gene products of the common subtypes. Instead, these products have been strongly implicated in xenobiotic metabolism and redox homeostasis through interactions of FANCC with cytochrome P-450 reductase and with glutathione S-transferase, and of FANCG with cytochrome P-450 2E1, as well as redox-dependent signalling through an interaction between FANCA and Akt kinase. We hypothesise that FA proteins act directly (via FANCC and FANCG) and indirectly (via FANCA, BRCA2 and FANCD2) with the machinery of cellular defence to modulate oxidative stress. The latter interactions may co-ordinate the link between the response to DNA damage and oxidative stress parameters (3, 6-12).
Pagano
Giovanni
G
Italian National Cancer Institute, G. Pascale Foundation, Paediatric Oncology Research Centre, via M. Semmola, I-80131 Naples, Italy. gbpagano@tin.it
Youssoufian
Hagop
H
D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology*; D005199:Fanconi Anemia / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000502:physiology*; D009687:Nuclear Proteins; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C497651:FANCC protein, human; C499909:FANCG protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019392:Cytochrome P-450 CYP2E1; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen