Download Fanconi Anemia Research Fund, Inc.

FANCD2
& the Fanconi Anemia Tumor Suppressor Pathway
Shayna Purcell
Joo et al., 333 (6040): 312-316
Fanconi anemia (FA) is a rare autosomal recessive
disorder characterized by genomic instability
Moldovan and D’Andrea, Annu. Rev. Genet. 2009.43:224
Disruption of the FA pathway causes
chromosomal breakages and hypersensitivity to
DNA interstrand crosslinks (ICLs)
Deans, Nature Reviews Cancer 11, 467-480 (July 2011)
Chang, BMC Medical Genomics. 2014;7:24
Clinical features of the disorder include:
developmental defects, early-onset bone
marrow failure & cancer predisposition
Fanconi Anemia Research Fund, Inc.
Fanconi Anemia: Guidelines for Diagnosis and Management (2008)
Following DNA damage, ATR activates the FA
core complex; FANCD2-I is ubiquitinated and
localized to chromatin foci
Wang, Nature Structural & Molecular Biology 15, 1128 - 1130 (2008)
FANCD2 ubiquitination
initiates DNA repair
through Nucleotide Excision
Repair, Translesion
Synthesis, and Homologous
Recombination
Ghosal and Chen, Translational Cancer Research, Vol 2, No 3 (June 2013)
In mice: Fancd2-null mutant phenotype
includes microphtalmia, perinatal lethality,
and tumor development
Houghtaling, Genes & Development, 17:2021–2035 © 2003
In humans: splicing mutations of FANCD2
predominate, leading to residual FANCD2 protein
in cells
Kalb, the American Journal of Human Genetics, Vol. 80, Issue 5, p895–910, May 2007
Long-term treatments of FA: blood and marrow
stem cell transplant, androgen therapy, synthetic
growth factors, or gene therapy
MacMillan, November 15, 2013; Blood: 122 (21)
References
"Fanconi Anemia, Complementation Group D2; FANCD2." Online Mendelian Inheritance in Man.
Johns Hopkins University, 26 June 1992. Web. 19 Mar. 2015.
"FA Fact Sheet." Fanconi Anemia Research Fund, Inc. 1 Feb. 2014. Web. 20 Mar. 2015.
Houghtaling, Scott. "Epithelial Cancer in Fanconi Anemia Complementation Group D2 (Fancd2)
Knockout Mice." Genes & Development 17 (2003): 2021-035. Cold Spring Harbor Laboratory Press. Web. 18 Mar.
2015.
"How Is Fanconi Anemia Treated?" NIH National Heart, Lung and Blood Institute. U.S. Department of
Health & Human Services, 1 Nov. 2011. Web. 26 Mar. 2015.
Kalb, Reinhard. "Hypomorphic Mutations in the Gene Encoding a Key Fanconi Anemia Protein,
FANCD2, Sustain a Significant Group of FA-D2 Patients With Severe Phenotype." American Journal of Human
Genetics 80.5 (2007): 895-910. ScienceDirect. Web. 22 Mar. 2015.
Moldovan, George-Lucian, and Alan D. D'Andrea. "How the Fanconi Anemia Pathway Guards the
Genome." Annual Review of Genetics 43 (2009): 223-49. Annual Reviews. Web. 19 Mar. 2015.
Pickering, Anna et al. “Advances in the Understanding of the Fanconi Anemia Tumor Suppressor
Pathway.” Cancer Biology & Therapy 14.12 (2013): 1089–1091. PMC. Web. 26 Mar. 2015.