Human Molecular Genetics, 2002, Vol. 11, No. 21 2591-2597
© 2002 Oxford University Press
BRCA1 interacts directly with the Fanconi anemia protein FANCA
1Department of Molecular and Medical Genetics and 2Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USA and 3Department of Pediatric Oncology, Dana-Farber Cancer Institute and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Received April 12, 2002; Accepted July 27, 2002
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.
* To whom correspondence should be addressed: Tel: +1 5034946881; Fax: +1 5034946882; Email: mosesr{at}ohsu.edu
The authors wish it to be known that, in their opinion, the first two authors should be considered as joint First Authors.
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