Document Type
Article
Publication Date
4-15-2005
Description
The BRCA2 breast cancer tumor suppressor is involved in the repair of double strand breaks and broken replication forks by homologous recombination through its interaction with DNA repair protein Rad51. Cells defective in BRCA2-FANCD1 are extremely sensitive to mitomycin C (MMC) similarly to cells deficient in any of the Fanconi anemia (FA) complementation group proteins (FANC). These observations suggest that the FA pathway and the BRCA2 and Rad51 repair pathway may be linked, although a functional connection between these pathways in DNA damage signaling remains to be determined. Here, we systematically investigated the interaction between these pathways. We show that in response to DNA damage, BRCA2-dependent Rad51 nuclear focus formation was normal in the absence of FANCD2 and that FANCD2 nuclear focus formation and mono-ubiquitination appeared normal in BRCA2-deficient cells. We report that the absence of BRCA2 substantially reduced homologous recombination repair of DNA breaks, whereas the absence of FANCD2 had little effect. Furthermore, we established that depletion of BRCA2 or Rad51 had a greater effect on cell survival in response to MMC than depletion of FANCD2 and that depletion of BRCA2 in FANCD2 mutant cells further sensitized these cells to MMC. Our results suggest that FANCD2 mediates double strand DNA break repair independently of Rad51-associated homologous recombination.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Ohashi, Akihiro; Zdzienicka, Malgorzata Z.; Chen, Junjie; and Couch, Fergus J.. 2005. Fanconi Anemia Complementation Group D2 (FANCD2) Functions Independently of BRCA2- and RAD51-Associated Homologous Recombination in Response to DNA Damage. Journal of Biological Chemistry. Vol.280(15). 14877-14883. https://doi.org/10.1074/jbc.M414669200 PMID: 15671039 ISSN: 0021-9258
Copyright Statement
© 2005 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
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