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

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 homozy...

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Bibliographic Details
Published in:Human molecular genetics 2001-02, Vol.10 (4), p.423-429
Main Authors: MEDHURST, Annette L, HUBER, Pia A. J, WAISFISZ, Quinten, DE WINTER, Johan P, MATHEW, Christopher G
Format: Article
Language:English
Subjects:
Anemias. Hemoglobinopathies
Animals
Biological and medical sciences
Cell Cycle Proteins
Diseases of red blood cells
DNA-Binding Proteins
FANCA protein
FANCC protein
FANCE gene
FANCE protein
FANCF gene
FANCF protein
FANCG protein
Fanconi Anemia - genetics
Fanconi Anemia - metabolism
Fanconi Anemia - pathology
Fanconi Anemia Complementation Group A Protein
Fanconi Anemia Complementation Group C Protein
Fanconi Anemia Complementation Group F Protein
Fanconi Anemia Complementation Group Proteins
Hematologic and hematopoietic diseases
Humans
Medical sciences
Mice
Nuclear Proteins
Precipitin Tests
Protein Binding - genetics
Proteins - genetics
Proteins - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Saccharomyces cerevisiae
Signal Transduction - genetics
Two-Hybrid System Techniques
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Summary: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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/10.4.423