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Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage

Blount, Benjamin C., Mack, Matthew M., Wehr, Carol M., MacGregor, James T., Hiatt, Robert A., Wang, Gene, Wickramasinghe, Sunitha N., Everson, Richard B., Ames, Bruce N.·1997·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.94.7.3290
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Abstract

Folate deficiency causes massive incorporation of uracil into human DNA (4 million per cell) and chromosome breaks. The likely mechanism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DNA by DNA polymerase. During repair of uracil in DNA, transient nicks are formed; two opposing nicks could lead to chromosome breaks. Both high DNA uracil levels and elevated micronucleus frequency (a measure of chromosome breaks) are reversed by folate administration. A significant proportion of the U.S. population has low folate levels, in the range associated with elevated uracil misincorporation and chromosome breaks. Such breaks could contribute to the increased risk of cancer and cognitive defects associated with folate deficiency in humans.

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Metadata

Authors
Blount, B. C., Mack, M. M., Wehr, C. M., MacGregor, J. T., Hiatt, R. A., Wang, G., Wickramasinghe, S. N., Everson, R. B., & Ames, B. N.
Affiliations
Department of Cell and Molecular Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720; Toxicology Laboratory, SRI International, Menlo Park, CA 94025; Division of Research, Kaiser Permanente Medical Care Program, Oakland CA 94611; Department of Haematology, St. Mary’s Hospital Medical School, Imperial College of Science, Technology and Medicine, London W21PG, United Kingdom; Karmanos Cancer Institute, and Department of Internal Medicine and...
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1997-04
Volume
94
Issue
7
Pages
3290-3295
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.94.7.3290
Cited by
1,139
References
0
Language
en

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