Hydrogen-bonding interaction of urea with DNA bases: A density functional theory study

Qiu, Zaozao; Xia, Yo.; Wang, H.; Diao, Kai-Sheng

doi:10.1134/s0022476611030036

Cited by 10 publications

(5 citation statements)

References 28 publications

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“…Optimization and frequency calculations for all monomers and base pairs were performed at the B3LYP/6-31G(d,p) level of theory. B3LYP has been previously successfully used to study the effects of nucleobase methylation on the A:T and G:C base pairs, , as well as the base-pairing properties for a range of other DNA lesions (see, e.g., refs − ). Subsequently, the binding energies were determined using B3LYP-D3 with Becke-Johnson (BJ) damping and the 6-311++G(2df,2p) basis set.…”

Section: Computational Detailsmentioning

confidence: 99%

Quantum Chemical Studies of the Structure and Stability of N-Methylated DNA Nucleobase Dimers: Insights into the Mutagenic Base Pairing of Damaged DNA

2017

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DNA is constantly under attack from exogenous and endogenous sources that modify the chemical structure of the nucleobases. A common type of nucleobase damage is N-methylation, which can result in mutagenesis. Nevertheless, these lesions are often repaired by the DNA repair enzyme AlkB, albeit at varying rates. Herein we use density functional theory (B3LYP-D3(BJ)/6-311++G(2df,2p)//B3LYP/6-31G(d,p)) to comprehensively examine the structural and energetic properties of base pairs between seven nucleobase lesions resulting from N-methylation on the Watson-Crick (WC) binding face and each canonical nucleobase. By characterizing 105 stable nucleobase dimers, we provide fundamental details regarding the preferred lesion base pairings. Specifically, we reveal that the flexibility of the methylamino group resulting from methylation of an exocyclic amino substituent allows the 2MeG, 4MeC, and 6MeA lesions to maintain a preference for canonical WC base pairing, which correlates with the experimentally reported lack of mutagenicity for these damage products. In contrast, calculated distortions in key structural parameters and altered binding energies for base pairs involving adducts formed upon methylation of a ring nitrogen (namely, 1MeG, 3MeT, 1MeA, and 3MeC) help rationalize the associated mutagenicity and repair efficiencies. Most importantly, our work provides molecular-level information about the interactions between N-methylated and canonical nucleobases that is critical for future large-scale modeling of damaged DNA and enzyme-DNA complexes that strive to further uncover the mutagenicity and repair propensities of these detrimental lesions.

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Section: Computational Detailsmentioning

confidence: 99%

Quantum Chemical Studies of the Structure and Stability of N-Methylated DNA Nucleobase Dimers: Insights into the Mutagenic Base Pairing of Damaged DNA

2017

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“…Thus, it was pointed out that TMAO preferentially binds to proteins (20,21), but, unlike urea, it does not induce a dehydration effect, such that the corresponding new mechanism was called ''preferential attraction'' (11). Despite the vast amount of literature on cosolute effects on proteins and the influence of salt ions on nucleobase conformations (29,30), the interaction of DNA with cosolutes was only sparsely investigated (26,28,(31)(32)(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular Dynamics Study

Oprzeska-Zingrebe

Smiatek

2018

Biophysical Journal

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In nature, a wide range of biological processes such as transcription termination and intermolecular binding depend on the formation of specific DNA secondary and tertiary structures. These structures can be both stabilized or destabilized by different cosolutes coexisting with nucleic acids in the cellular environment. In our molecular dynamics simulation study, we investigate the binding of urea at different concentrations to short 7-nucleotide single-stranded DNA structures in aqueous solution. The local concentration of urea around a native DNA hairpin in comparison to an unfolded DNA conformation is analyzed by a preferential binding model in light of the Kirkwood-Buff theory. All our findings indicate a pronounced accumulation of urea around DNA that is driven by a combination of electrostatic and dispersion interactions and accomplished by a significant replacement of hydrating water molecules. The outcomes of our study can be regarded as a first step into a deeper mechanistic understanding toward cosolute-induced effects on nucleotide structures in general.

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“…Moreover, we observed a strong interaction between the urea molecules and the DNA. Likewise, Qiu et al also found a strong interaction of the hydrogen bond between the urea molecules and DNA bases 42 . Hence, it seems reasonable to assume that urea can bind directly to oocyte genetic material and cause oxidative damage to DNA 43 .…”

Section: Discussionmentioning

confidence: 90%

A multilevel analysis identifies the different relationships between amino acids and the competence of oocytes matured individually or in groups

Kowsar

Mansouri

Sadeghi

et al. 2020

Sci Rep

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High-protein diets contribute to an increase in urea follicular concentrations associated with decreased fertility. Urea has been shown to interfere with the epidermal growth factor (EGF)/EGFR system, which has been shown to have a beneficial effect during in vitro maturation (IVM) of oocytes. Of note, the number of cumulus-oocyte complexes (COCs) in the maturation medium can change the maturation and the developmental competence of COCs. Therefore, it was hypothesized that, the presence of urea and EGF may have a differential effect on the depletion/appearance of AAs and competence of COCs matured individually (I-IVM system) or in groups (G-IVM system). In the G-IVM system, COCs increased consumption (depletion) of AAs compared with other groups in the presence of high-level urea (40 mg/dl) + EGF (10 ng/ml). In the I-IVM system, the non-cleaved COCs depleted more AAs than the cleaved COCs, in particular in the presence of urea. The combination of urea and EGF increased the depletion of AAs in the G-IVM system. However, the EGF abrogated the urea-induced depletion of AAs by the I-IVM COCs. The use of N-acetyl-l-cysteine as an EGFR inhibitor canceled urea-induced depletion of AAs. This shows the inhibiting effect of urea over the EGF/EGFR system. In the presence of urea + EGF, COCs had a lower degree of developmental competence than control in both I- and G-IVM systems. Arginine had the best predictive power to identify highly competent COCs in the G-IVM system, while glutamine was the best predictor of the cleavage in the I-IVM system. In conclusion, this multi-level study shows that COCs matured individually or in groups may have different association with AAs metabolism. These findings provide new insights into the relationships between AA metabolism and the subsequent developmental competence of COCs.

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Hydrogen-bonding interaction of urea with DNA bases: A density functional theory study

Cited by 10 publications

References 28 publications

Quantum Chemical Studies of the Structure and Stability of N-Methylated DNA Nucleobase Dimers: Insights into the Mutagenic Base Pairing of Damaged DNA

Quantum Chemical Studies of the Structure and Stability of N-Methylated DNA Nucleobase Dimers: Insights into the Mutagenic Base Pairing of Damaged DNA

Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular Dynamics Study

A multilevel analysis identifies the different relationships between amino acids and the competence of oocytes matured individually or in groups

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