BRCA1 interacts directly with the Fanconi anemia protein FANCA

Alexandra Folias, Mara Matkovic, Donald Bruun, Sonja Reid, James Hejna, Markus Grompe, Alan D'Andrea, Robb Moses

Research output: Contribution to journalArticle

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Abstract

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 coimmunoprecipitatlon 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.

Original languageEnglish (US)
Pages (from-to)2591-2597
Number of pages7
JournalHuman Molecular Genetics
Volume11
Issue number21
StatePublished - Oct 1 2002

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Fanconi Anemia Complementation Group Proteins
Fanconi Anemia
BRCA1 Protein
Fanconi Anemia Complementation Group A Protein
Fanconi Anemia Complementation Group D2 Protein
DNA Damage
Chromosomal Instability
Cell Extracts
S Phase
GTP-Binding Proteins
DNA Repair
Anemia
Leukemia
Yeasts
DNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Folias, A., Matkovic, M., Bruun, D., Reid, S., Hejna, J., Grompe, M., ... Moses, R. (2002). BRCA1 interacts directly with the Fanconi anemia protein FANCA. Human Molecular Genetics, 11(21), 2591-2597.

BRCA1 interacts directly with the Fanconi anemia protein FANCA. / Folias, Alexandra; Matkovic, Mara; Bruun, Donald; Reid, Sonja; Hejna, James; Grompe, Markus; D'Andrea, Alan; Moses, Robb.

In: Human Molecular Genetics, Vol. 11, No. 21, 01.10.2002, p. 2591-2597.

Research output: Contribution to journalArticle

Folias, A, Matkovic, M, Bruun, D, Reid, S, Hejna, J, Grompe, M, D'Andrea, A & Moses, R 2002, 'BRCA1 interacts directly with the Fanconi anemia protein FANCA', Human Molecular Genetics, vol. 11, no. 21, pp. 2591-2597.
Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M et al. BRCA1 interacts directly with the Fanconi anemia protein FANCA. Human Molecular Genetics. 2002 Oct 1;11(21):2591-2597.
Folias, Alexandra ; Matkovic, Mara ; Bruun, Donald ; Reid, Sonja ; Hejna, James ; Grompe, Markus ; D'Andrea, Alan ; Moses, Robb. / BRCA1 interacts directly with the Fanconi anemia protein FANCA. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 21. pp. 2591-2597.
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