Human Genetics

, Volume 67, Issue 2, pp 136–142

DNA polymerase α inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes

Authors

  • Thomas W. Glover
    • The Genetics Center of Southwest Biomedical Research Institute
  • Carol Berger
    • The Genetics Center of Southwest Biomedical Research Institute
  • Jane Coyle
    • The Genetics Center of Southwest Biomedical Research Institute
  • Barbara Echo
    • The Genetics Center of Southwest Biomedical Research Institute
Original Investigations

DOI: 10.1007/BF00272988

Cite this article as:
Glover, T.W., Berger, C., Coyle, J. et al. Hum Genet (1984) 67: 136. doi:10.1007/BF00272988

Summary

Aphidicolin, a specific inhibitor of DNA polymerase α, is known to induce chromosomal aberrations. At concentrations that did not greatly affect mitotic index, aphidicolin induced a striking number of chromosome gaps and breaks distributed in a highly nonrandom manner in cultured human lymphocytes. Specific chromosome bands, especially 2q31, 3p14, 6q26, 7q32, 16q23, and Xp22 were preferentially damaged in lymphocytes from each of 12 subjects studied. Total and site-specific damage was dose dependent and greatly increased when folic acid was removed from the medium. The sites most sensitive to aphidicolin damage include the “hot spots” seen under conditions of thymidylate stress and in studies of spontaneous chromosomal damage. The fragile X site, which can also be induced by thymidylate stress, was not induced by aphidicolin in lymphocytes, suggesting a separate mechanism for its induction. Aphidicolin represents a novel tool for detection of hot spots on human chromosomes through the mechanism of DNA polymerase α inhibition. The hot spots induced by aphidicolin represent a new class of fragile sites which we term common fragile sites.

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Copyright information

© Springer-Verlag 1984