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

作　　者：张兴华[1] 肖彬[1] 侯锡苗[1] 徐春华[1] 王鹏业[1] 李明[1] 

机构地区：[1]中国科学院物理研究所北京凝聚态物理国家实验室,北京100190

出　　处：《物理学报》2009年第6期4301-4306,共6页Acta Physica Sinica

基　　金：国家自然科学基金(批准号:30870590;10834014)资助的课题~~

摘　　要：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.

关 键 词：顺铂 DNA凝聚 单分子操纵 抗癌药 

分 类 号：Q75[生物学—分子生物学]