Molecular biology of Fanconi anaemia--an old problem, a new insight.
Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a complex mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double-strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation.
Ahmad
Shamim I
SI
Department of Life Sciences, Nottingham Trent University, UK. Shamim.ahmad@ntu.ac.uk
Hanaoka
Fumio
F
Kirk
Sandra H
SH
D017209:Apoptosis; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D010100:Oxygen