Cisplatin induces loop structures and condensation of single DNA molecules

• Published in: Nucleic acids research 2009-04, Vol.37 (5), p.1400-1410
• Main Authors: Hou, Xi-Miao, Zhang, Xing-Hua, Wei, Kong-Ji, Ji, Chao, Dou, Shuo-Xing, Wang, Wei-Chi, Li, Ming, Wang, Peng-Ye
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Bacteriophage lambda - genetics; Cisplatin - pharmacology; DNA - chemistry; DNA - drug effects; DNA - ultrastructure; DNA, Viral - chemistry; DNA, Viral - drug effects; DNA, Viral - ultrastructure; Elasticity; Microscopy, Atomic Force; Molecular Biology; Nucleic Acid Conformation; Organoplatinum Compounds - pharmacology; Oxaliplatin
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkn933

Structural properties of single λ DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from ∼52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed. Based on experimental results from both single-molecule and AFM studies, we propose a model to explain this kind of DNA condensation by cisplatin: first, di-adducts induce local distortions of DNA. Next, micro-loops of ∼20 nm appear through distant crosslinks. Then, large aggregates are formed through further crosslinks. Finally, DNA is condensed into a compact globule. Experiments with Pt(dach)Cl2 indicate that oxaliplatin may modify the DNA structures in the same way as cisplatin. The observed loop structure formation of DNA may be an important feature of the effect of platinum anti-cancer drugs that are analogous to cisplatin in structure.