用单分子磁镊研究顺铂导致的DNA凝聚

Study of cisplatin-induced DNA compaction using single molecule magnetic tweezers

本文报道了用单分子磁镊研究抗癌药顺铂导致的DNA凝聚过程.结果表明,当拉力比较小时,DNA凝聚的长度-时间曲线是连续缩短和阶跃缩短并存的复杂曲线.而当拉力较大但又不足以阻止DNA的凝聚时,凝聚曲线为连续缩短的双曲线.增加顺铂浓度只会增大凝聚速度而不会改变反应曲线的形状.实验结果与下列成环凝聚模型一致:在水溶液中顺铂能够与DNA形成双臂加合物,也能形成单臂加合物.当顺铂使DNA长链上相距较远的碱基间发生远程交联时,形成小环,导致DNA凝聚.小环间的进一步交联会引起DNA的完全凝聚.DNA凝聚产物十分稳定.

We report a single molecule study on cisplatin-induced DNA compaction. It is found that, at a small external tension （ 〈 1 pN）, the DNA compaction time course is irregular with many continuous shortening processes and abrupt large size jumps. The time course becomes smooth and hyperbolic when the external tension increases to a moderate value, which is not large enough to inhibit the compaction. The time course depends on the external tension rather than the concentration of cisplatin; the latter only influences the compaction rate. The results are consistent with a looping-and-cross-linking compaction model. Namely, in aqueous solutions, cisplatin forms both monoadducts and diadducts with DNA. When cisplatin induces distant cross-links between DNA bases, micro-loops are formed, which make DNA compact. Further cross-linking between the micro-loops leads to complete compaction of DNA. In addition, the compacted DNA structure is quite stable.