Nucleic Acids Research Advance Access published online on January 7, 2009
Nucleic Acids Research, doi:10.1093/nar/gkn933
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Molecular Biology |
Cisplatin induces loop structures and condensation of single DNA molecules
Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
* To whom correspondence should be addressed. Tel: +86-10-82649569; Fax: +86-10-82640224 Email: pywang{at}aphy.iphy.ac.cn
Received August 10, 2008. Revised October 28, 2008. Accepted November 5, 2008.
Structural properties of single 
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.