| Literature References | 1. STRATHDEE, C.A., GAVISH, H., SHANNON, W.R. AND BUCHWALD, M.
Cloning of cDNAs for Fanconi's anaemia by functional complementation.
NATURE 356 763-767 (1992).
2. GIBSON, R.A., BUCHWALD, M., ROBERTS, R.G. AND MATHEW, C.G.
Characterisation of the exon structure of the Fanconi anaemia group
C gene by vectorette PCR.
HUM.MOL.GENET. 2(1) 35-38 (1993).
3. WALSH, C.E., NIENHUIS, A.W., SAMULSKI, R.J., BROWN, M.G., MILLER, J.L.,
YOUNG, N.S. AND LIU, J.M.
Phenotypic correction of Fanconi anemia in human hematopoietic cells
with a recombinant adeno-associated virus vector.
J.CLIN.INVEST. 94 1440-1448 (1994).
4. YOUSSOUFIAN, H.
Localization of Fanconi anemia C protein to the cytoplasm of
mammalian cells.
PROC.NATL.ACAD.SCI.U.S.A. 91 7975-7979 (1994).
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| Documentation | Fanconi anaemia (FA) [1-3] is a recessive inherited disease characterised by
defective DNA repair. FA cells are sensitive to DNA cross-linking agents
that cause chromosomal instability and cell death. The disease is manifested
clinically by progressive pancytopenia, variable physical anomalies, and
predisposition to malignancy [3]. Four complementation groups have been
identified, designated A to D. The gene for group C (FACC) has been cloned.
Expression of the FACC cDNA corrects the phenotypic defect of FA(C) cells,
resulting in normalized cell growth in the presence of DNA cross-linking
agents such as mitomycin C (MMC) [3]. Gene transfer of the FACC gene should
provide a survival advantage to transduced hematopoietic cells, suggesting
that FA might be an ideal candidate for gene therapy [3].
The function of the FACC gene is not known. Immunofluorescence and sub-
cellular fractionation studies of human cell lines, and COS-7 cells
transiently expressing human FACC, showed the protein to be located
primarily in the cytoplasm [4]. Yet, placement of a nuclear localisation
signal at the N-terminus of FACC directed the hybrid protein to the nuclei
of transfected COS-7 cells. Such findings suggest an indirect role for FACC
in regulating DNA repair in this group of Fanconi anaemia [4].
FANCONICGENE is a 9-element fingerprint that provides a signature for
Fanconi anaemia group C gene product. The fingerprint was derived from
an initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning the full alignment length. Two iterations on OWL26.3 were
required to reach convergence, at which point a true set comprising 4
sequences was identified.
An update on SPTR37_9f identified a true set of 4 sequences.
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