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Cellular Oncology - Volume 28 2006, Issue 1-2, Pages 3-29

Review Division of Clinical Genetics and Human Genetics, VU Medical Center, van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands



Copyright © 2006 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Fanconi anemia FA, a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failure, hypersensitivity to DNA cross-linking agents, chromosomal instability and susceptibility to cancer. At least 12 genetic subtypes have been described FA-A, B, C, D1, D2, E, F, G, I, J, L, M and all except FA-I have been linked to a distinct gene. Most FA proteins form a complex that activates the FANCD2 protein via monoubiquitination, while FANCJ and FANCD1-BRCA2 function downstream of this step. The FA proteins typically lack functional domains, except for FANCJ-BRIP1 and FANCM, which are DNA helicases, and FANCL, which is probably an E3 ubiquitin conjugating enzyme. Based on the hypersensitivity to cross-linking agents, the FA proteins are thought to function in the repair of DNA interstrand cross-links, which block the progression of DNA replication forks. Here we present a hypothetical model, which not only describes the assembly of the FA pathway, but also positions this pathway in the broader context of DNA cross-link repair. Finally, the possible role for the FA pathway, in particular FANCF and FANCB, in the origin of sporadic cancer is discussed.





Author: Marieke Levitus, Hans Joenje, and Johan P. de Winter

Source: https://www.hindawi.com/



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