Fanconi anemia: genetic analysis of a human disease using chicken system - PubMed (original) (raw)
Fanconi anemia: genetic analysis of a human disease using chicken system
M Takata et al. Cytogenet Genome Res. 2007.
Abstract
Fanconi anemia (FA) is a rare hereditary disorder characterized by skeletal abnormalities, bone marrow failure, and an increased incidence of cancer. The basic cellular abnormality in FA has been postulated to lie in the DNA repair mechanisms because cells from FA patients display chromosomal breakage, which is particularly remarkable following induction of DNA crosslinks. However, experimental evidence for this hypothesis has been lacking. To test whether DNA repair is really defective in FA cells, we disrupted several FA genes in chicken B cell line DT40. By measuring efficiency of gene conversion and hypermutation at the Immunoglobulin locus, we have shown that DT40 FA mutant cell lines exhibited defects in homologous DNA recombination, and possibly, translesion synthesis. However, levels of sister chromatid exchange, another important cellular event mediated by HR, were not reduced, possibly indicating the role of FA genes only in a subpathway of HR. Our results indicate that chicken DT40 cells could be highly useful in molecular dissection of basic biochemical processes, which are deficient in a human genetic disorder.
Copyright 2007 S. Karger AG, Basel.
Similar articles
- The Fanconi anemia pathway: insights from somatic cell genetics using DT40 cell line.
Takata M, Ishiai M, Kitao H. Takata M, et al. Mutat Res. 2009 Jul 31;668(1-2):92-102. doi: 10.1016/j.mrfmmm.2008.12.012. Epub 2009 Jan 17. Mutat Res. 2009. PMID: 19622405 Review. - FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.
Wilson JB, Yamamoto K, Marriott AS, Hussain S, Sung P, Hoatlin ME, Mathew CG, Takata M, Thompson LH, Kupfer GM, Jones NJ. Wilson JB, et al. Oncogene. 2008 Jun 12;27(26):3641-52. doi: 10.1038/sj.onc.1211034. Epub 2008 Jan 21. Oncogene. 2008. PMID: 18212739 - New insights into the Fanconi anemia pathway from an isogenic FancG hamster CHO mutant.
Tebbs RS, Hinz JM, Yamada NA, Wilson JB, Salazar EP, Thomas CB, Jones IM, Jones NJ, Thompson LH. Tebbs RS, et al. DNA Repair (Amst). 2005 Jan 2;4(1):11-22. doi: 10.1016/j.dnarep.2004.06.013. DNA Repair (Amst). 2005. PMID: 15533833 - Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins XRCC3 and BRCA2.
Hussain S, Wilson JB, Blom E, Thompson LH, Sung P, Gordon SM, Kupfer GM, Joenje H, Mathew CG, Jones NJ. Hussain S, et al. DNA Repair (Amst). 2006 May 10;5(5):629-40. doi: 10.1016/j.dnarep.2006.02.007. Epub 2006 Apr 18. DNA Repair (Amst). 2006. PMID: 16621732 - The Fanconi anaemia/BRCA pathway.
D'Andrea AD, Grompe M. D'Andrea AD, et al. Nat Rev Cancer. 2003 Jan;3(1):23-34. doi: 10.1038/nrc970. Nat Rev Cancer. 2003. PMID: 12509764 Review.
Cited by
- The phenotype of FancB-mutant mouse embryonic stem cells.
Kim TM, Ko JH, Choi YJ, Hu L, Hasty P. Kim TM, et al. Mutat Res. 2011 Jul 1;712(1-2):20-7. doi: 10.1016/j.mrfmmm.2011.03.010. Epub 2011 Mar 30. Mutat Res. 2011. PMID: 21458466 Free PMC article. - How the fanconi anemia pathway guards the genome.
Moldovan GL, D'Andrea AD. Moldovan GL, et al. Annu Rev Genet. 2009;43:223-49. doi: 10.1146/annurev-genet-102108-134222. Annu Rev Genet. 2009. PMID: 19686080 Free PMC article. Review. - Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights.
Thompson LH, Hinz JM. Thompson LH, et al. Mutat Res. 2009 Jul 31;668(1-2):54-72. doi: 10.1016/j.mrfmmm.2009.02.003. Epub 2009 Feb 21. Mutat Res. 2009. PMID: 19622404 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources