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Human Molecular Genetics, 2001, Vol. 10, No. 4 423-429
© 2001 Oxford University Press

Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway

Annette L. Medhurst1, Pia A.J. Huber1, Quinten Waisfisz2, Johan P. de Winter2 and Christopher G. Mathew1,+

1Division of Medical and Molecular Genetics, Guy’s, King’s and St Thomas’ School of Medicine, 8th Floor, Guy’s Tower, Guy’s Hospital, London SE1 9RT, UK and 2Department of Clinical Genetics and Human Genetics, Free University, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands

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.

+ To whom correspondence should be addressed. Tel: +44 20 7955 4653; Fax: +44 20 7955 4644; Email: christopher.mathew@kcl.ac.uk


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Home page
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[Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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A Multiprotein Nuclear Complex Connects Fanconi Anemia and Bloom Syndrome
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51
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Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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Home page
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Home page
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