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, Karl Sperling

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1121-1126
Number of pages6
JournalCarcinogenesis
Volume23
Issue number7
StatePublished - 2002

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Fanconi Anemia
DNA Repair
Fanconi Anemia Complementation Group D2 Protein
BRCA2 Protein
Fibroblasts
Recombinational DNA Repair
Gastrin-Secreting Cells
Chromosomal Instability
Diploidy
Protein Isoforms
Complementary DNA
Antibodies
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Digweed, M., Rothe, S., Demuth, I., Scholz, R., Schindler, D., Stumm, M., ... Sperling, K. (2002). Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. Carcinogenesis, 23(7), 1121-1126.

Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. / Digweed, Martin; Rothe, Susanne; Demuth, Ilja; Scholz, Regina; Schindler, Detlev; Stumm, Markus; Grompe, Markus; Jordan, Andreas; Sperling, Karl.

In: Carcinogenesis, Vol. 23, No. 7, 2002, p. 1121-1126.

Research output: Contribution to journalArticle

Digweed, M, Rothe, S, Demuth, I, Scholz, R, Schindler, D, Stumm, M, Grompe, M, Jordan, A & Sperling, K 2002, 'Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia', Carcinogenesis, vol. 23, no. 7, pp. 1121-1126.
Digweed M, Rothe S, Demuth I, Scholz R, Schindler D, Stumm M et al. Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. Carcinogenesis. 2002;23(7):1121-1126.
Digweed, Martin ; Rothe, Susanne ; Demuth, Ilja ; Scholz, Regina ; Schindler, Detlev ; Stumm, Markus ; Grompe, Markus ; Jordan, Andreas ; Sperling, Karl. / Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. In: Carcinogenesis. 2002 ; Vol. 23, No. 7. pp. 1121-1126.
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