Human fragile site FRA16B DNA excludes nucleosomes in the presence of distamycin.
Human fragile sites are weak staining gaps in chromosomes generated by specific culture conditions. The short CGG repeating DNA derived from folate-sensitive fragile sites has been shown to exclude single nucleosomes. To test whether this nucleosome exclusion model provides a general molecular mechanism for the formation of fragile sites, a different class of fragile site, the 33-base pair AT-rich repeating DNAs derived from the rare distamycin-inducible site, FRA16B, was examined for its ability to assemble single nucleosomes and nucleosome arrays using in vitro nucleosome reconstitution methods. The FRA16B DNA fragments strongly exclude nucleosome assembly only in the presence of distamycin, and increasing the number of 33-bp repeats increases the effect of distamycin in the destabilization of the nucleosome formation, suggesting a common mechanism for the formation of fragile sites.
Hsu
Ying Ying
YY
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
Wang
Yuh-Hwa
YH
D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D001667:Binding, Competitive; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002885:Chromosomes, Human, Pair 16; D004247:DNA / Q000378:metabolism; D004214:Distamycins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion
D000998:Antiviral Agents; D004214:Distamycins; D009707:Nucleosomes; C030000:stallimycin; D004247:DNA