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Fanconi anemia group A and D cell lines respond normally to inhibitors of cell cycle regulation

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Somatic Cell and Molecular Genetics

Abstract

Cells from patients with Fanconi anemia (FA) show decreased viability and decreased chromosome stability after treatment with DNA cross-linking agents, compared to normal cells. FA cells also show a relative accumulation at the G2/M transition after such treatment. This has suggested a possible checkpoint abnormality. In the studies presented here, treatment with hydroxyurea, caffeine or inhibitors of cell cycle kinases did not reveal abnormalities in survival or chromosome stability in FA-A or FA-D cells. Chromosomal breaks introduced by hydrogen peroxide or methyl methanesulfonate accumulated to the same extent in FA-A or FA-D cells as in normal cells. We conclude that FA-A and FA-D cells respond normally to agents known to alter the cell cycle or introduce DNA strand breaks. FA cells process strand breaks and a variety of DNA monoadducts normally. Our results are compatible with repair of DNA crosslinks being slower in FA than in normal cells and FA cells having normal cell cycle checkpoints.

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Authors and Affiliations

  1. Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Mail Code: L103, 97201, Portland, Oregon

    Patrick Johnstone, Carol Reifsteck, Susan Kohler, Susan Olson & Robb E. Moses

  2. Mitotix Inc., Cambridge, Massachusetts

    Peter Worland

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  1. Patrick Johnstone
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  2. Carol Reifsteck
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  3. Susan Kohler
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  4. Peter Worland
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  5. Susan Olson
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  6. Robb E. Moses
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Johnstone, P., Reifsteck, C., Kohler, S. et al. Fanconi anemia group A and D cell lines respond normally to inhibitors of cell cycle regulation. Somat Cell Mol Genet 23, 371–377 (1997). https://doi.org/10.1007/BF02673747

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  • DOI: https://doi.org/10.1007/BF02673747

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