Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site
Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site
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DOI：
10.1073/pnas.95.14.8141
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Kerem, B
中科院分区：
文献类型：
--
作者：
Mishmar, D;Rahat, A;Kerem, B
常见的脆性位点是容易断裂和重排的染色体位点，假设为外源DNA整合提供靶点。我们克隆了一个猿猴病毒40整合位点，并通过荧光原位杂交分析表明，整合事件发生在一个共同的aphidicolin诱导的人类7号染色体上的脆性位点，FRA 7 H。在FRA 7 H的161 kb区域内发现了几个可能具有异常DNA结构的区域，包括高柔性、低稳定性和非B-DNA形成序列。我们对已发表的FRA 3B序列和推定的部分FRA 7 G进行了类似的分析，这也揭示了一个令人印象深刻的具有高灵活性和低稳定性的区域簇。因此，这些不寻常的DNA特征可能是常见的脆性位点的内在属性，可能会影响它们的复制和凝聚以及组织，并可能导致脆弱性。
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.