Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1.
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.
Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden, The Netherlands.
Barbara C
BC
Godthelp
Fré
F
Artwert
Hans
H
Joenje
Małgorzata Z
MZ
Zdzienicka
D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D051135:Rad51 Recombinase; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; C495153:RAD51 protein, human; D051135:Rad51 Recombinase