On the nature of folic-acid-sensitive fragile sites in human chromosomes: an hypothesis.
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. It is hypothesized that folate-sensitive fragile sites on chromosomes 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.
D001482:Base Composition; D002843:Chromatin / Q000378:metabolism; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002877:Chromosomes, Human / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D009698:Nucleoproteins / Q000378:metabolism; D013941:Thymine / Q000378:metabolism; D014498:Uracil / Q000378:metabolism
D002843:Chromatin; D009698:Nucleoproteins; D014498:Uracil; D004247:DNA; D005492:Folic Acid; D013941:Thymine