Fanconi anaemia (FA) is an autosomal recessive inherited disorder associated 
with a progressive aplastic anaemia, diverse congenital abnormalities and 
cancer. The condition is genetically heterogeneous, with at least seven 
complementation groups (A-G) described. Cells from individuals who are 
homozygous for mutations in FA genes are characterized by chromosomal 
instability and hypersensitivity to DNA interstrand crosslinking agents. These 
features suggest a possible role for the encoded proteins in the recognition or 
repair of these lesions, but neither their function nor whether they operate in 
a concerted or discrete functional pathways is known. The recent cloning of the 
FANCF and FANCE genes has allowed us to investigate the interaction of the 
proteins encoded by five of the seven complementation groups of FA. We used the 
yeast two-hybrid system and co-immunoprecipitation analysis to test the 10 
possible pairs of proteins for direct interaction. In addition to the previously 
described binding of FANCA to FANCG, we now demonstrate direct interaction of 
FANCF with FANCG, of FANCC with FANCE and a weaker interaction of FANCE with 
both FANCA and FANCG. These findings show that the newly identified FANCE 
protein is an integral part of the FA pathway, and support the concept of a 
functional link between all known proteins encoded by the genes that are mutated 
in this disorder. These proteins may act either as a multimeric complex or by 
sequential recruitment of subsets of the proteins in a common pathway that 
protects the genomic integrity of mammalian cells.