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Related Experiment Videos

Excess thymidine induces folate sensitive fragile sites.

G R Sutherland, E Baker, A Fratini

    American Journal of Medical Genetics
    |October 1, 1985
    PubMed
    Summary

    Folate-sensitive fragile sites in human chromosomes can be induced by thymidine. Revised biochemical understanding shows low nucleotide levels trigger fragile site expression, suggesting a DNA sequence model.

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    Area of Science:

    • Genetics
    • Molecular Biology
    • Human Chromosomes

    Background:

    • Folate-sensitive fragile sites are specific regions on human chromosomes.
    • Previous research indicated induction by certain substances, but the precise biochemical mechanisms were unclear.

    Purpose of the Study:

    • To investigate the induction of folate-sensitive fragile sites in human chromosomes.
    • To clarify the biochemical pathways involved in fragile site expression.
    • To propose a structural model for DNA at fragile sites.

    Main Methods:

    • Induction of fragile sites in cultured human lymphocytes using thymidine and BrdU.
    • Biochemical analysis of nucleotide triphosphate levels.
    • Development of a DNA sequence model for fragile sites.

    Main Results:

    • High levels of thymidine, but not BrdU, induced folate-sensitive fragile sites.
    • Low levels of thymidylate or deoxycytidine triphosphate were identified as triggers for fragile site expression.
    • A model proposing alternating polypurine/polypyrimidine sequences at fragile sites was developed.

    Conclusions:

    • The induction of folate-sensitive fragile sites is linked to specific nucleotide triphosphate pool imbalances.
    • A revised biochemical model explains fragile site expression.
    • Alternating polypurine/polypyrimidine sequences are proposed as the structural basis for fragile sites.

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