On the nature of folic‐acid‐sensitive fragile sites in human chromosomes: An hypothesis
- 1 September 1983
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics
- Vol. 16 (1), 23-28
- https://doi.org/10.1002/ajmg.1320160105
Abstract
The methyl groups of thymine and 5-methylcytosine exposed along the major groove of the DNA double helix are involved in the binding of specific proteins to specific DNA regions. Folate-sensitive fragile sites on chromosomes may appear as a result of heritable defects of DNA methylation along a region normally binding a folding protein involved in chromosome condensation. Impairment of DNA-folding-protein interaction would result. A superimposed folate deficiency, or any condition leading to impaired thymidylate biosynthesis, would promote misincorporation into DNA of uracil in place of thymine, thus producing a further loss of methyl groups at the fragile site and eventually precluding a full DNA-folding-protein interaction. A localized collapse of the chromosome structure would follow.Keywords
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