Biallelic Inactivation of BRCA2 in Fanconi Anemia

@article{Howlett2002BiallelicIO,
  title={Biallelic Inactivation of BRCA2 in Fanconi Anemia},
  author={Niall G. Howlett and Toshiyasu Taniguchi and Susan B. Olson and B Cox and Quinten Waisfisz and Christine E M de Die-Smulders and Nicole S. Persky and Markus Grompe and Hans Joenje and Gerard Pals and H Ikeda and Edward Fox and Alan D. D’Andrea},
  journal={Science},
  year={2002},
  volume={297},
  pages={606 - 609}
}
Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-typeBRCA2 complementary DNA restores MMC… Expand
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TLDR
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References

SHOWING 1-10 OF 26 REFERENCES
Positional cloning of a novel Fanconi anemia gene, FANCD2.
TLDR
Retroviral transduction of the cloned FANCD2 cDNA into FA-D2 cells resulted in functional complementation of MMC sensitivity, and the positional cloning of FAN CD2 was reported. Expand
Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
TLDR
The FANCD2 protein provides the missing link between the FA protein complex and the cellular BRCA1 repair machinery, and results in the cellular and clinical phenotype common to all FA subtypes. Expand
Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9
TLDR
Results suggest that mutations in at least four different genes lead to FA, a degree of genetic heterogeneity comparable to that of other DNA repair disorders. Expand
Evidence for at least eight Fanconi anemia genes.
TLDR
Three new groups are defined,FA-F, FA-G, and FA-H, providing evidence for a minimum of eight distinct FA genes, as well as indicating nonidentity with group E. Expand
Convergence of the Fanconi Anemia and Ataxia Telangiectasia Signaling Pathways
TLDR
The Fanconi anemia protein, FANCD2, is identified as a link between the FA and ATM damage response pathways and independent posttranslational modifications regulating discrete cellular signaling pathways are identified. Expand
Complementation analysis in Fanconi anemia: assignment of the reference FA-H patient to group A.
TLDR
Evidence is presented indicating that the patient who has been the sole representative of the eighth complementation group (FA-H) in fact belongs to group FA-A, and future assignment of patients with FA to new complementation groups should conform with more-stringent criteria. Expand
The emerging genetic and molecular basis of Fanconi anaemia
TLDR
The recent cloning of most of the FA-associated genes, and the characterization of their protein products, has provided tantalizing clues as to the molecular basis of this disease. Expand
Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification
TLDR
It is reported that Brca2(Tr2014/Tr2014) MEFs frequently develop micronuclei, suggesting a potential mechanism whereby loss of BRCA2 may, within subclones, drive the loss of cell-cycle regulation genes, enabling proliferation and tumourigenesis. Expand
Involvement of Brca2 in DNA repair.
TLDR
Findings define a function of Brca2 in DNA repair, whose loss precipitates replicative failure, mutagen sensitivity, and genetic instability reminiscent of Bloom syndrome and Fanconi anemia. Expand
Reassessment of cancer predisposition of Fanconi anemia heterozygotes.
The hypothesis that heterozygotes for the Fanconi anemia (FA) gene are predisposed to cancer was investigated by comparing the observed and expected numbers of cancer cases and deaths in 25 extendedExpand
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