Toledo F, Coquelle A, Svetlova E, Debatisse M
Unité de Génétique Somatique (URA CNRS 1960), Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Nucleic Acids Res. 2000 Dec 1;28(23):4805-13. doi: 10.1093/nar/28.23.4805.
Common fragile sites are chromosomal loci prone to breakage and rearrangement that can be induced by aphidicolin, an inhibitor of DNA polymerases. Within these loci, sites of preferential DNA breaks were proposed to correlate with peaks of enhanced DNA flexibility, the function of which remains elusive. Here we show that mammalian DNA replication origins are enriched in peaks of enhanced flexibility. This finding suggests that the search for these features may help in the mapping of replication origins, and we present evidence supporting this hypothesis. The association of peaks of flexibility with replication origins also suggests that some origins may associate with minor levels of fragility. As shown here, an increased sensitivity to aphidicolin was found near two mammalian DNA replication origins.
常见脆性位点是染色体上易于断裂和重排的位点，可被DNA聚合酶抑制剂阿非迪霉素诱导产生。在这些位点中，优先发生DNA断裂的位点被认为与DNA灵活性增强的峰值相关，但其功能仍不清楚。在此，我们表明哺乳动物DNA复制起点富含灵活性增强的峰值。这一发现表明，寻找这些特征可能有助于复制起点的定位，并且我们提供了支持这一假设的证据。灵活性峰值与复制起点的关联还表明，一些起点可能与较低水平的脆性相关。如此处所示，在两个哺乳动物DNA复制起点附近发现对阿非迪霉素的敏感性增加。
