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The FANCC Gene and Its Products

  • Susan M. Gordon
  • Manuel Buchwald
Chapter
  • 416 Downloads
Part of the Medical Intelligence Unit book series

Abstract

Fanconi anaemia (FA) is an autosomal recessive disorder characterized by progressive pancytopaenia and predisposition to malignancy, often accompanied by congenital malformations. The cellular phenotype of FA includes increased chromosomal instability and accumulation in the G2 phase of the cell cycle, both of which are exacerbated by the hallmark sensitivity of FA cells to DNA crosslinking agents such as mitomycin C (MMC) and diepoxybutane (DEB). FA is genetically heterogeneous, consisting of at least eleven complementation groups, the genes for eight of which have been cloned. FANCC was the first gene causal for FA to be identified, and consequently has been the most intensively studied. Loss of function studies have demonstrated an important role for FANCC in the proliferation of germ cells and haematopoietic stem cells (HPCs). Together with the protein products of at least five other FA genes, FANCC participates in the formation of a nuclear protein complex, the formation of which is required for monoubiquitination of the FANCD2 protein. This cooperative action of the FA proteins fits well with the indistinguishable clinical presentation and universal cellular crosslinker sensitivity of the complementation groups. However, despite its ability to participate in a nuclear protein complex and possible involvement in nuclear activities such as DNA repair and transcriptional regulation, FANCC is unique among the FA proteins in having a predominandy cytoplasmic cellular localization. Investigation of possible cytoplasmic roles for FANCC have revealed it to be a multifunctional protein involved in the suppression of cell death in response to a wide range of stimuli including DNA-crosslinking agents, factor withdrawl, dsRNA, stimulatory cytokines and Fas ligation, as well as a having a possibly interrelated role in maintaining of the redox state of the cell.

Keywords

Fanconi Anemia Promyelocytic Leukemia Zinc Finger Nevoid Basal Cell Carcinoma Syndrome Haematopoietic Progenitor Cell Fanconi Anaemia Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Eurekah.com and Springer Science+Business Media 2006

Authors and Affiliations

  • Susan M. Gordon
    • 1
  • Manuel Buchwald
    • 2
  1. 1.Program in Genetics and Genomic Biology, Research InstituteHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Molecular and Medical GeneticsUniversity of TorontoTorontoCanada

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