Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site

Dan Mishmar, Ayelet Rahat, Stephen W. Scherer, Gerald Nyakatura, Bernd Hinzmann, Yoshinori Kohwi, Yael Mandel-Gutfroind, Jeffrey R. Lee, Bernd Drescher, Dean E. Sas, Hanah Margalit, Mattias Platzer, Aryeh Weiss, Lap Chee Tsui, André Rosenthal, Batsheva Kerem

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192 Scopus citations

Abstract

Common fragile sites are chromosomal loci prone to breakage and rearrangement, hypothesized to provide targets for foreign DNA integration. We cloned a simian virus 40 integration site and showed by fluorescent in situ hybridization analysis that the integration event had occurred within a common aphidicolin-induced fragile site on human chromosome 7, FRA7H. A region of 161 kb spanning FRA7H was defined and sequenced. Several regions with a potential unusual DNA structure, including high-flexibility, low- stability, and non-B-DNA-forming sequences were identified in this region. We performed a similar analysis on the published FRA3B sequence and the putative partial FRA7G, which also revealed an impressive cluster of regions with high flexibility and low stability. Thus, these unusual DNA characteristics are possibly intrinsic properties of common fragile sites that may affect their replication and condensation as well as organization, and may lead to fragility.

Original languageEnglish
Pages (from-to)8141-8146
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number14
DOIs
StatePublished - 7 Jul 1998
Externally publishedYes

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