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Current Knowledge on the Pathophysiology of Fanconi Anemia: From Genes to Phenotypes

Authors
  • Yamashita, Takayuki1
  • Nakahata, Tatsutoshi2
  • 1 Institute of Medical Science, University of Tokyo, Division of Genetic Diagnosis, Tokyo , Tokyo
  • 2 Kyoto University, Department of Pediatrics, Faculty of Medicine, Kyoto, Japan , Kyoto (Japan)
Type
Published Article
Journal
International Journal of Hematology
Publisher
Springer-Verlag
Publication Date
Jul 01, 2001
Volume
74
Issue
1
Pages
33–41
Identifiers
DOI: 10.1007/BF02982547
Source
Springer Nature
Keywords
License
Yellow

Abstract

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, bone marrow failure, and leukemia susceptibility. FA cells show chromosome instability and hypersensitivity to DNA cross-linking agents such as mito-mycin C. Recent studies indicate that there are at least 8 genetically distinct FA groups (A, B, C, D1, D2, E, F, G). To date, 6 genes (for A, C, D2, E, F, and G) have been cloned. In this review, we describe the structures and functions of FA proteins. Increasing evidence indicates that the multiple FA proteins cooperate in a biochemical pathway and/or a multimer complex. FANCD2, a downstream component of the FA pathway, has recently been shown to be ubiquitinated in response to DNA damage and to translocate to nuclear foci containing BRCA1, a breast cancer susceptibility gene product, suggesting a role for this protein in DNA repair functions. We also describe 2 emerging issues: genotype-phenotype relationships and mosaicism. The FA pathway is likely to play a critical role as a caretaker of genomic integrity in hematopoietic stem cells. Clarifying the molecular basis of this disease may provide new insights into the pathogenesis of bone marrow failure syndromes and myeloid malignancies.

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