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Volume 272, Number 37, Issue of September 12, 1997 pp. 23328-23333
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Elevated Homologous Recombination Activity in Fanconi Anemia Fibroblasts

(Received for publication, February 19, 1997, and in revised form, July 7, 1997)

Bhaskar Thyagarajan and Colin Campbell

From the Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

It is widely believed that Fanconi anemia cells possess a reduced ability to repair inter-strand DNA cross-links. While the mechanism through which inter-strand DNA cross-links are removed from mammalian chromosomes is unknown, these lesions are repaired via homologous recombination in lower eukaryotes and bacteria. Based on the hypothesis that a similar mechanism of DNA repair functions in mammalian somatic cells, we measured homologous recombination activity in diploid fibroblasts from healthy donors, and Fanconi anemia patients. Somewhat surprisingly, homologous recombination levels in nuclear protein extracts prepared from Fanconi anemia cells were nearly 100-fold higher than in extracts prepared from control cells. We observed a similar increase in the activity of a 100-kDa homologous DNA pairing protein in extracts from Fanconi anemia cells. Transfection studies confirmed that plasmid homologous recombination levels in intact Fanconi anemia cells were substantially elevated, compared with control cells. These results suggest that inappropriately elevated levels of homologous recombination activity may contribute to the genomic instability and cancer predisposition that characterize Fanconi anemia.


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