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Metal ion-nucleic acid interactions contribute substantially to the structure and biological activity of nucleic acids and have a wide range of potential applications in nanotechnology. In this study, we examined the interactions between metal ions and mismatched base pairs in duplex DNA to reveal the underlying molecular mechanism. UV melting analyses showed that the melting temperature ( T m ) of a 21-base pair duplex DNA with each of the C-A, C-C and C-T mismatched base pairs increased upon the addition of Ag + . However, isothermal titration calorimetry (ITC) demonstrated that Ag + only bound to the C-C mismatched base pair of the duplex DNA to form C-Ag-C bonds, without binding to the C-A and C-T mismatches. These results showed that T m increased even when metal ions did not bind to the mismatched base pairs of the duplex DNA. Although the increase in T m upon the addition of the metal ions is often used to detect metal ion binding to mismatched base pairs of duplex DNA, these results indicated that UV melting analyses are unable to detect the direct binding of metal ions to the mismatched base pairs. Because ITC analyses directly detect the heat derived from metal ion binding to mismatched base pairs of duplex DNA, we concluded that this may be an effective detection approach.

Metal ion-nucleic acid interactions contribute significantly to nucleic acid structure and biological activity and have potential applications in nanotechnology. Hg 2+ specifically binds to the natural T-T mismatched base pair in duplex DNA to form a T-Hg-T base pair. Metal ions may enhance DNA damage induced by DNA-damaging agents, such as oxidative agents. The interactions between metal ions and damaged DNAs, such as mismatched oxidized bases, have not been well characterized. Here, we examined the possibility of Hg 2+ binding to an asymmetric mismatched base pair involving thymine and 5-hydroxyuracil (OHdU), an oxidized base produced by the oxidative deamination of cytosine. UV melting analyses showed that only the melting temperature of the single T-OHdU mismatched duplex DNA increased upon Hg 2+ addition. CD spectra indicated no significant change in the higher-order structure of the single T-OHdU mismatched duplex DNA upon Hg 2+ addition. X-ray crystallographic structure with two consecutive T-OHdU mismatched base pairs and isothermal titration calorimetric analyses with the single T-OHdU mismatched base pair showed that Hg 2+ specifically binds to the N3 positions of both T and OHdU in T-OHdU at 1:1 molar ratio, with a 5×10 5 M -1 binding constant of to form the T-Hg-OHdU base pair. The Hg 2+ -bound structure and the Hg 2+ -binding affinity for T-OHdU was similar to those for T-T. This study on T-Hg-OHdU metal-mediated base pair could aid in studying the molecular mechanism of metal ion-mediated DNA damage and their potential applications in nanotechnology., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

A 68-year-old man was noted to have an abnormal shadow on chest X-ray. Chest computed tomography (CT) showed a 100 mm mass in the lower right thoracic cavity. The mass was lobulated and compressed the surrounding lung tissue and diaphragm. Contrast-enhanced CT showed that the mass was heterogeneously enhanced and contained expanded blood vessels within it. The expanded vessels communicated with the pulmonary artery and vein via the diaphragmatic surface of the right lung. The mass was diagnosed as a solitary fibrous tumor of the pleura (SFTP) by CT-guided lung biopsy. We performed partial resection of the lung including the tumor via right eighth intercostal lateral thoracotomy. Intraoperative examination showed that the tumor was pediculated from the diaphragmatic surface of the right lung. The stem was about 3 cm long and easily cut with a stapler. The tumor was definitively diagnosed as a malignant SFTP. No recurrence was found for 12 months postoperatively.