In this paper the interactions between DNA and anti-cancer drug oxaliplatin were investigated by using magnetic tweezers.The dynamics of DNA condensation due to oxaliplatin was traced under various forces.It is found that torsion constraint in DNA enhances the ability of oxaliplatin for shortening DNA.The transplatin helps oxaliplatin combine to DNA and increase the rate of DNA condensation.All these results are consistent to the previously proposed model and are helpful for further investigation of interaction between DNA and oxaliplatin.
T7 RNA polymerase can transcribe DNA to RNA by translocating along the DNA. Structural studies suggest that the pivoting rotation of the O helix in the fingers domain may drive the movement of the O helix C-terminal Tyr639 from pre- to post-translocation positions. In a series of all-atom molecular dynamics simulations, we show that the movement of Tyr639 is not tightly coupled to the rotation of the O helix, and that the two processes are only weakly dependent on each other. We also show that the internal potential of the enzyme itself generates a small difference in free energy (△E) between the post- and pre-translocation positions of Tyr639. The calculated value of △E is consistent with that obtained from single-molecule experimental data. These findings lend support to a model in which the translocation takes place via a Brownian ratchet mechanism, with the small free energy bias △E arising from the conformational change of the enzyme itself.
Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.
RecQ5β is an essential DNA helicase in humans, playing important roles in DNA replication, repair, recombination and transcription. The unwinding activity and substrate specificity of RecQ5β is still elusive. Here, we used stopped-flow kinetic method to measure the unwinding and dissociation kinetics of RecQ5β with several kinds of DNA substrates, and found that RecQ5β could well unwind ss/ds DNA, forked DNA and Holiday junction, but was compromised in unwinding blunt DNA and G-quadruplex. Rec5β has the preferred unwinding specificity for certain DNA substrates containing the junction point, which may improve the binding affinity and unwinding activity of RecQ5β. Moreover, from a comparison with the truncated RecQ5β~(1-467), we discovered that the C-terminal domain might strongly influence the unwinding activity and binding affinity of RecQ5β. These results may shed light on the physiological functions and working mechanisms of RecQ5β helicase.