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Abstract: 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.