Fanconi anemia (FA) is a rare autosomal recessive disease characterized by 
skeletal defects, anemia, chromosomal instability and increased risk of 
leukemia. At the cellular level FA is characterized by increased sensitivity to 
agents forming interstrand crosslinks (ICL) in DNA. Six FA genes have been 
cloned and interactions among individual FANC proteins have been found. The 
FANCD2 protein co-localizes in nuclear foci with the BRCA1 protein following DNA 
damage and during S-phase, requiring the FANCA, C, E and G proteins to do so. 
This finding may reflect a direct role for the BRCA1 protein in double strand 
break (DSB) repair and interaction with the FANC proteins. Therefore 
interactions between BRCA1 and the FANC proteins were investigated. Among the 
known FANC proteins, we find evidence for direct interaction only between the 
FANCA protein and BRCA1. The evidence rests on three different tests: yeast 
two-hybrid analysis, coimmunoprecipitation from in vitro synthesis, and 
coimmunoprecipitation from cell extracts. The amino terminal portion of FANCA 
and the central part (aa 740-1083) of BRCA1 contain the sites of interaction. 
The interaction does not depend on DNA damage, thus FANCA and BRCA1 are 
constitutively interacting. The demonstrated interaction directly connects BRCA1 
to the FA pathway of DNA repair.