Human Fragile Site FRA16B DNA Excludes Nucleosomes in the
Presence of Distamycin*
Ying Ying
Hsu and
Yuh-Hwa
Wang
From the Department of Biochemistry, Robert Wood Johnson Medical
School, University of Medicine and Dentistry of New Jersey,
Piscataway, New Jersey 08854
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.
*
This work was supported by Public Health Service Grant
CA85826 from the National Cancer Institute.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.