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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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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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