Journal Article

Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia

Martin Digweed, Susanne Rothe, Ilja Demuth, Regina Scholz, Detlev Schindler, Markus Stumm, Markus Grompe, Andreas Jordan and Karl Sperling

in Carcinogenesis

Volume 23, issue 7, pages 1121-1126
Published in print July 2002 | ISSN: 0143-3334
Published online July 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.7.1121
Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia

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The role of the Fanconi anaemia genes in DNA repair was examined by a quantitative analysis of nuclear DNA repair foci in FA primary fibroblasts after ionising irradiation using antibodies directed against RAD51, MRE11 and BRCA1 for visualisation. IR induced foci detected with anti-RAD51, but not those detected with anti-MRE11, are reduced in fibroblasts of all eight FA complementation groups in comparison to control cells. Correction of FA-A, FA-C and FA-G cells by retroviral cDNA transfer specifically corrected the RAD51-foci response but did not affect formation of foci containing BRCA1 or MRE11. Since all FA cells, except FA-D1, lack the monoubiquitinated FANCD2-L protein, this isoform is likely to be involved in the formation of nuclear foci containing RAD51 in diploid FA cells. FA-D1 cells show the same attenuation in RAD51 foci formation, suggesting that the unknown FANCD1 protein is similarly involved in RAD51 foci formation, either independently or as a subsequent step in the FANCD2 pathway. These findings indicate that Fanconi anaemia cells have an impairment in the RAD51-dependent homologous recombination pathway for DNA repair, explaining their chromosomal instability and extreme sensitivity to DNA cross-linking agents.

Keywords: DSB, double strand break; EGFP, enhanced green fluorescence protein; FA, Fanconi anemia; IR, ionising radiation; PBS, phosphatebuffered saline

Journal Article.  5290 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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