Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow
failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin
C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic
integrity. Fujiwara et al. (1977) presented evidence that Fanconi anemia fibroblasts have an impaired capacity of removing DNA
interstrand crosslinks induced by mitomycin C. They favored the view that a DNA crosslink repair deficiency is
responsible for chromosomal damage in this disorder.
NCBI Summary:
The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group C. [provided by RefSeq, Jul 2008]
General function
Cell death/survival, DNA Replication
Comment
Strathdee et al. (1992) stated that at least 4 complementation
groups had been identified in Fanconi anemia. Using a functional complementation method, they cloned cDNAs that corrected
the defect of group C cells. The cDNAs encoded alternatively processed transcripts of a new gene, designated FACC, that is
mutated in group C patients. The predicted FACC polypeptide did not contain any motifs common to other proteins and so
represents a new gene involved in cellular response to DNA damage. FACC transcripts were detected in a wide variety of
tissues and cell lines by use of PCR with reverse-transcribed RNA
Cellular localization
Nuclear
Comment
Ovarian function
Germ cell development
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Expression regulated by
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Ovarian localization
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Follicle stages
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Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment:Whitney MA,et al 1996 reported germ cell defects and hematopoietic hypersensitivity to gamma-interferon in
mice with a targeted disruption of the Fanconi anemia C gene.
Mutant mice had normal neonatal
viability and gross morphology, but their cells had the expected chromosome breakage and DNA
cross-linker sensitivity. Surprisingly, male and female mutant mice had reduced numbers of germ cells
and females had markedly impaired fertility. No anemia was detectable in the peripheral blood during
the first year of life, but the colony forming capacity of marrow progenitor cells was abnormal in vitro
in mutant mice. Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma.
This previously unrecognized phenotype may form the basis for BM failure in human FA.
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: Fanconi anemia (FA) is an autosomal recessive chromosome instability syndrome characterized by
progressive bone marrow (BM) failure, skeletal defects, and increased susceptibility to malignancy.
FA cells are hypersensitive to DNA cross-linking agents, oxygen and have cell cycle abnormalities.
Berkovitz et al. (1984) concluded that abnormal sexual development in Fanconi anemia represents hypergonadotropic
hypogonadism.