Dataset Information

Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

ABSTRACT: Ion-mediated interaction between DNAs is essential for DNA condensation, and it is generally believed that monovalent and nonspecifically binding divalent cations cannot induce the aggregation of double-stranded (ds) DNAs. Interestingly, recent experiments found that alkaline earth metal ions such as Mg²⁺ can induce the aggregation of triple-stranded (ts) DNAs, although there is still a lack of deep understanding of the surprising findings at the microscopic level. In this work, we employed all-atom dynamic simulations to directly calculate the potentials of mean force (PMFs) between tsDNAs, between dsDNAs, and between tsDNA and dsDNA in Mg²⁺ solutions. Our calculations show that the PMF between tsDNAs is apparently attractive and becomes more strongly attractive at higher [Mg²⁺], although the PMF between dsDNAs cannot become apparently attractive even at high [Mg²⁺]. Our analyses show that Mg²⁺ internally binds into grooves and externally binds to phosphate groups for both tsDNA and dsDNA, whereas the external binding of Mg²⁺ is much stronger for tsDNA. Such stronger external binding of Mg²⁺ for tsDNA favors more apparent ion-bridging between helices than for dsDNA. Furthermore, our analyses illustrate that bridging ions, as a special part of external binding ions, are tightly and positively coupled to ion-mediated attraction between DNAs.

SUBMITTER: Zhang ZL

PROVIDER: S-EPMC5549645 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

Zhang Zhong-Liang ZL Wu Yuan-Yan YY Xi Kun K Sang Jian-Ping JP Tan Zhi-Jie ZJ

Biophysical journal 20170801 3

Ion-mediated interaction between DNAs is essential for DNA condensation, and it is generally believed that monovalent and nonspecifically binding divalent cations cannot induce the aggregation of double-stranded (ds) DNAs. Interestingly, recent experiments found that alkaline earth metal ions such as Mg<sup>2+</sup> can induce the aggregation of triple-stranded (ts) DNAs, although there is still a lack of deep understanding of the surprising findings at the microscopic level. In this work, we em ...[more]

PMID: 28793207

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Project description:DNA interstrand cross-links have important biological consequences and are useful biotechnology tools. Phenylselenyl substituted derivatives of thymidine (1) and 5-methyl-2'-deoxycytidine (5) produce interstrand cross-links in duplex DNA when oxidized by NaIO4. The mechanism involves a [2,3]-sigmatropic rearrangement of the respective selenoxides to the corresponding methide type intermediates, which ultimately produce the interstrand cross-links. Determination of the rate constants for the selenoxide rearrangements indicates that the rate-determining step for cross-linking is after methide formation. Cross-linking by the thymidine derivative in duplex DNA shows a modest kinetic preference when flanked by pyrimidines as opposed to purines. In contrast, the rate constant for cross-link formation from 5 opposite dG in duplex DNA is strongly dependent upon the flanking sequence and, in general, is at least an order of magnitude slower than that for 1 in an otherwise identical sequence. Introduction of mispairs at the base pairs flanking 5 or substitution of the opposing dG by dI significantly increases the rate constant and yield for cross-linking, indicating that stronger hydrogen bonding between the methide derived from it and dG compared to dA and the respective electrophile derived from 1 limits reaction by increasing the barrier to rotation into the required syn-conformation. Incorporation of 1 or 5 in triplex forming oligonucleotides (TFOs) that utilize Hoogsteen base pairing also yields interstrand cross-links. The dC derivative produces ICLs approximately 10x faster than the thymidine derivative when incorporated at the 5'-termini of the TFOs and higher yields when incorporated at internal sites. The slower, less efficient ICL formation emanating from 1 is attributed to reaction at N1-dA, which requires local melting of the duplex. In contrast, 5 produces cross-links by reacting with N7-dG. The cross-linking reactions of 1 and 5 illustrate the versatility and utility of these molecules as mechanistic probes and tools for biotechnology.

Dataset Information

Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

Publications

Divalent Ion-Mediated DNA-DNA Interactions: A Comparative Study of Triplex and Duplex.

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