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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Hejna, M. Holtorf, J. Hines, L. Mathewson, A. Hemphill, M. Al-Dhalimy, S. B. Olson, and R. E. Moses Tip60 Is Required for DNA Interstrand Cross-link Repair in the Fanconi Anemia Pathway J. Biol. Chem., April 11, 2008; 283(15): 9844 - 9851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Barroso, R.L. Milne, L.P. Fernandez, P. Zamora, J.I. Arias, J. Benitez, and G. Ribas FANCD2 associated with sporadic breast cancer risk Carcinogenesis, September 1, 2006; 27(9): 1930 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhu and A. Dutta An ATR- and BRCA1-Mediated Fanconi Anemia Pathway Is Required for Activating the G2/M Checkpoint and DNA Damage Repair upon Rereplication Mol. Cell. Biol., June 15, 2006; 26(12): 4601 - 4611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Cheng, R. Kusumoto, P. L. Opresko, X. Sui, S. Huang, M. L. Nicolette, T. T. Paull, J. Campisi, M. Seidman, and V. A. Bohr Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links. Nucleic Acids Res., January 1, 2006; 34(9): 2751 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Yang, Z. Herceg, K. Nakanishi, I. Demuth, C. Piccoli, J. Michelon, G. Hildebrand, M. Jasin, M. Digweed, and Z.-Q. Wang The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells Carcinogenesis, October 1, 2005; 26(10): 1731 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Furuta, X. Jiang, B. Gu, E. Cheng, P.-L. Chen, and W.-H. Lee Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells PNAS, June 28, 2005; 102(26): 9176 - 9181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ohashi, M. Z. Zdzienicka, J. Chen, and F. J. Couch Fanconi Anemia Complementation Group D2 (FANCD2) Functions Independently of BRCA2- and RAD51-associated Homologous Recombination in Response to DNA Damage J. Biol. Chem., April 15, 2005; 280(15): 14877 - 14883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Kennedy, J. E. Quinn, P. B. Mullan, P. G. Johnston, and D. P. Harkin The Role of BRCA1 in the Cellular Response to Chemotherapy J Natl Cancer Inst, November 17, 2004; 96(22): 1659 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hussain, J. B. Wilson, A. L. Medhurst, J. Hejna, E. Witt, S. Ananth, A. Davies, J.-Y. Masson, R. Moses, S. C. West, et al. Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways Hum. Mol. Genet., June 15, 2004; 13(12): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Brodeur, I. Goulet, C. S. Tremblay, C. Charbonneau, M.-C. Delisle, C. Godin, C. Huard, E. W. Khandjian, M. Buchwald, G. Levesque, et al. Regulation of the Fanconi Anemia Group C Protein through Proteolytic Modification J. Biol. Chem., February 6, 2004; 279(6): 4713 - 4720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hohenstein and R. Fodde Of mice and (wo)men: genotype-phenotype correlations in BRCA1 Hum. Mol. Genet., October 15, 2003; 12(90002): R271 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hussain, E. Witt, P. A.J. Huber, A. L. Medhurst, A. Ashworth, and C. G. Mathew Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1 Hum. Mol. Genet., October 1, 2003; 12(19): 2503 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C.Y. Wong, N. Alon, C. Mckerlie, J. R. Huang, M. S. Meyn, and M. Buchwald Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia Hum. Mol. Genet., August 15, 2003; 12(16): 2063 - 2076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tonnies, S. Huber, J.-S. Kuhl, A. Gerlach, W. Ebell, and H. Neitzel Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor Blood, May 15, 2003; 101(10): 3872 - 3874. [Abstract] [Full Text] [PDF]
|
|