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Review
. 2009 Apr;23(2):193-214.
doi: 10.1016/j.hoc.2009.01.008.

Fanconi anemia

Allison M Green  1 , Gary M Kupfer
Affiliations
Review

Fanconi anemia

Allison M Green et al. Hematol Oncol Clin North Am. 2009 Apr.

Abstract

Fanconi anemia (FA) is an autosomal and X-linked recessive disorder characterized by bone marrow failure, acute myelogenous leukemia, solid tumors, and developmental abnormalities. Recent years have seen a dramatic improvement in FA patient treatment, resulting in a greater survival of children into adulthood. These improvements have been made despite the fact that a definitive cellular function for the proteins in the FA pathway has yet to be elucidated. Delineating the cellular functions of the FA pathway could help further improve the treatment options for FA patients and further reduce the probability of succumbing to the disease. This article reviews the current clinical aspects of FA including presentation, diagnosis, and treatment followed by a review of the molecular aspects of FA as they are currently understood.

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Figures

Figure 1
Figure 1. The FA pathway proteins
The FA pathway is composed of at least 13 genes. Each of these genes, when biallelically mutated, causes FA. The encoded proteins can be subdivided within the FA pathway into three groups: proteins that make up the core complex, the FANCD2 and FANCI proteins which compose the ID complex, and three downstream effector proteins: FANCD1/BRCA2, FANCJ/BRIP1/BACH1, and FANCN/PALB2. Following treatment with DNA crosslinking agents or during S phase of the cell cycle, FANCD2 and FANCI become monoubiquitylated. An intact core complex is required for these modifications which result in the translocation of the two proteins to chromatin within cells. Within chromatin, FANCD2 and FANCI colocalize with DNA repair proteins including the downstream effector FA proteins at sites of DNA damage in nuclear foci. FA proteins are in blue.
Figure 2
Figure 2. FA pathway functions
While an exact mechanism for the FA pathway has yet to be elucidated, it seems to function in sensing DNA damage induced by DNA crosslinking agents such as MMC and DEB likely plays some role in initiating DNA repair. A significant body of work has also pointed to a role for the FA pathway in cell signaling in response to stress stimuli and in apoptosis in the cytoplasm, affecting maintenance of the hematopoietic machinery so it is likely that at least some of these proteins are multifunctional.
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References

    1. Bagby GC, Alter BP. Fanconi Anemia. Semin Hematol. 2006;43(3):147–156. - PubMed
    1. D’Andrea AD, Dahl N, Guinan EC, et al. Marrow Failure. Hematology Am Soc Hematol Educ Program. 2002:58–72. - PubMed
    1. Tischkowitz M, Dokal I. Fanconi anaemia and leukemia- clinical and molecular aspects. Br J Haematol. 2004;126(2):176–191. - PubMed
    1. Alter BP. Fanconi’s anemia, transplantation, and cancer. Pediatr Transplant. 2005;9(Suppl 7):81–86. - PubMed
    1. Lustig JP, Lugassy G, Neder A, et al. Head and neck carcinoma in Fanconi’s anaemia--report of a case and review of the literature. Eur J Cancer B Oral Oncol. 1995;31B(1):68–72. - PubMed

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