FRA3B Extends Over a Broad Region and Contains a Spontaneous HPV16 Integration Site: Direct Evidence for the Coincidence of Viral Integration Sites and Fragile Sites

作者：Charles M. Wilke, Bryan K. Hall, Ann Hoge, William J. Paradee, David I. Smith, Thomas W. Glover · 发表于：Human Molecular Genetics · 年份：1996 · DOI：10.1093/hmg/5.2.187 · 被引用次数：244 · 研究领域：Genetics and Neurodevelopmental Disorders、Genomic variations and chromosomal abnormalities、RNA modifications and cancer

The common fragile site at 3p14.2 (FRA3B) is the most sensitive site on normal human chromosomes for the formation of gaps and breaks when DNA replication is perturbed by aphidicolin or folate stress. Although rare fragile sites are known to arise through the expansion of CCG repeats, the mechanism responsible for common fragile sites is unknown. Beyond being a basic component of chromosome structure, no biological effects of common fragile sites have been convincingly shown, although suggestions have been made that breakage and recombination at these sites may sometimes be mechanistically involved in deletions observed in many tumors and in constitutional deletions. In an observation related to the high rate of recombination at fragile sites, a number of studies have shown a statistical association between the integration of transforming DNA viruses and chromosomal fragile sites. Using FISH analysis we recently identified a 1.3 Mb YAC spanning both FRA3B and the t(3;8) translocation associated with hereditary RCC. Here we report the further localization of FRA3B within this YAC. Using lambda subclones of the YAC as FISH probes, gaps and breaks were found to occur over a broad region of at least 50 kb. Neither CCG nor CAG repeats were found in this region suggesting a different mechanism for fragility than seen with rare fragile sites. We further show that an area of frequent gaps and breaks within FRA3B, defined by a lambda contig, coincides with a previously characterized s...