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  • Title: [Fragile sites on human chromosomes and cancer-specific chromosomal rearrangements].
    Author: Hori T.
    Journal: Gan To Kagaku Ryoho; 1986 Mar; 13(3 Pt 2):667-76. PubMed ID: 3963838.
    Abstract:
    Heritable fragile sites are specific points on human chromosomes which appear as nonstaining gaps or breaks under certain physiological conditions and are inherited in a Mendelian codominant fashion. Recent findings of a correlation between fragile sites and breakpoints involved in specific chromosomal rearrangements seen in some neoplasias suggest that fragile sites may be unique sites particularly susceptible to chromosome breakage and rearrangement under in vivo physiological conditions. The majority of known fragile sites, including fragile X, are classified in the folate-sensitive group and are expressed under conditions of thymidylate stress. In thymidine-auxotrophic somatic cell hybrids constructed by cell fusion between fragile X cells and thymidylate synthase-negative mouse mutant cells, we have shown that thymidine deprivation alone can induce the expression of fragile X, suggesting that the primary DNA structure itself is responsible for its expression. Elucidation of the DNA structure of fragile sites may provide a clue to the understanding of genetic instability in the human genome and its possible involvement in cancer-specific chromosomal rearrangements.
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