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Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1

Oncogene volume 21, pages 5002–5005 (2002)Cite this article

Abstract

Fanconi anemia is a hereditary cancer susceptibility disorder characterized at the cellular level by spontaneous chromosomal instability and specific hypersensitivity to DNA cross-linking agents such as mitomycin C. This phenotype suggests a possible role for the Fanconi anemia proteins in the repair of DNA lesions induced by these agents, but the molecular mechanism underlying the defect in this disorder has not yet been identified. Here, we show that amongst eight so far identified complementation groups of Fanconi anemia, only fibroblasts derived from group D1 are defective in the formation of nuclear Rad51 foci after X-ray irradiation or mitomycin C treatment. This indicates that the FANCD1 gene product is uniquely involved in the assembly and/or stabilization of the Rad51 complex. Since DNA damage-induced Rad51 nuclear foci are thought to reflect repair of DNA double-strand breaks by homologous recombination, our results suggest that FANCD1 is likely to be involved in homologous recombination-dependent repair.

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Acknowledgements

We thank the FA families for participating; Dr FE Benson for providing the antibodies against Rad51; Drs M Buchwald and D Papadopoulo for providing F145, HSC230-F fibroblasts and HSC62 lymphoblasts and F van de Water for her technical assistance. Financial support was from the Netherlands Organization for Scientific Research (NWO, grant 901-01-190).

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Authors and Affiliations

  1. Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, AL Leiden, NL-2333, The Netherlands

    Barbara C Godthelp & Małgorzata Z Zdzienicka

  2. Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, BT Amsterdam, NL-1081, The Netherlands

    Fré Artwert & Hans Joenje

  3. Department of Molecular Cell Genetics, The Ludwik Rydygier University of Medical Sciences, Bydgoszcz, Poland

    Małgorzata Z Zdzienicka

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  1. Barbara C Godthelp
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  2. Fré Artwert
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  4. Małgorzata Z Zdzienicka
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Correspondence to Małgorzata Z Zdzienicka.

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Godthelp, B., Artwert, F., Joenje, H. et al. Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Oncogene 21, 5002–5005 (2002). https://doi.org/10.1038/sj.onc.1205656

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