Marcus model of spontaneous point mutation in DNA

Turaeva, N. N.; Brown-Kennerly, Victoria

doi:10.1016/j.chemphys.2015.09.005

Cited by 19 publications

(15 citation statements)

References 35 publications

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“…DPT reaction does not show any mutagenic effects. The structural mechanisms for spontaneous point mutations (Turaeva and Brown-Kennerly, 2015) in DNA occur through the transitions and transversions, and various enzymatic complexes for DNA lesions are involved in the repair process, such as DNA glycolases, polymerases, and photolyases (Fromme et al, 2004; Braithwaite et al, 2005). The stable canonical NAB pairs were studied to understand the mechanism of genetic code (Blancafort et al, 2005; Chen and Li, 2005; Marian, 2005; Perun et al, 2005; Tomić et al, 2005).…”

Section: Proton Transfer In Nucleobasesmentioning

confidence: 99%

The Role of Proton Transfer on Mutations

Srivastava

2019

Front. Chem.

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Hydrogen bonds play a critical role in nucleobase studies as they encode genes, map protein structures, provide stability to the base pairs, and are involved in spontaneous and induced mutations. Proton transfer mechanism is a critical phenomenon that is related to the acid–base characteristics of the nucleobases in Watson–Crick base pairs. The energetic and dynamical behavior of the proton can be depicted from these characteristics and their adjustment to the water molecules or the surrounding ions. Further, new pathways open up in which protonated nucleobases are generated by proton transfer from the ionized water molecules and elimination of a hydroxyl radical in this review, the analysis will be focused on understanding the mechanism of untargeted mutations in canonical, wobble, Hoogsteen pairs, and mutagenic tautomers through the non-covalent interactions. Further, rare tautomer formation through the single proton transfer (SPT) and the double proton transfer (DPT), quantum tunneling in nucleobases, radiation-induced bystander effects, role of water in proton transfer (PT) reactions, PT in anticancer drugs–DNA interaction, displacement and oriental polarization, possible models for mutations in DNA, genome instability, and role of proton transfer using kinetic parameters for RNA will be discussed.

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Section: Proton Transfer In Nucleobasesmentioning

confidence: 99%

The Role of Proton Transfer on Mutations

Srivastava

2019

Front. Chem.

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“…We established from the physico-chemical point of view that the generally accepted mechanism of the DPT along intermolecular H-bonds [22][23][24][25][26][27][28][29] cannot be the source of formation of mutagenic tautomers of DNA bases in the А•T(WC) and G•C(WC) Watson-Crick (socalled Löwdin's mechanism) [51][52][53] and G•T(w) wobble [54] base pairs, and also in the m 1 T•CH 3 COOH, m 9 A•CH 3 COOH, m 1 C•CH 3 COOH and m 9 G•CH 3 COOH complexes by the participation of DNA bases and side chains of the amino acids (m-methyl group) [55].…”

Section: Classical Mechanisms Of Dna Base Tautomerization Via Dpt Alomentioning

confidence: 99%

“…Despite great advances in experimental, in particular X-ray analysis [14,15], NMR, in particular relaxation dispersion measurements [11][12][13][16][17][18], and theoretical [19][20][21] investigations, there is no unique approach to the physico-chemical mechanisms enabling DNA bases in the canonical tautomeric form to acquire rare or mutagenic tautomeric form before the dissociation of the Watson-Crick nucleobase pairs into the monomers by the replication machinery in order to produce mispairs resulting in further misincorporations and as a result the spontaneous point mutations at the DNA replication. It is generally accepted in the literature that mutagenic tautomers of the DNA bases can arise via the double proton transfer (DPT) along intermolecular H-bonds in the Watson-Crick [22][23][24][25] and wobble [26] base pairs, and also in the protein-DNA complexes [27]. However, some authors also consider as the source of the origin of the spontaneous transitions the formation of the ionized DNA base pairs [28].…”

Section: Introductionmentioning

confidence: 99%

Renaissance of the Tautomeric Hypothesis of the Spontaneous Point Mutations in DNA: New Ideas and Computational Approaches

Brovarets’¹,

Hovorun²

2018

Mitochondrial DNA - New Insights

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In this chapter, we formulate basic physico-chemical principles that define the microstructural nature of the origin of the spontaneous incorporation and replication point errors-transitions and transversions-arising during DNA biosynthesis. At this point, we relied on the firstly discovered ability of the DNA base mispairs to tautomerize via the sequential intrapair proton transfer and highly stable, highly polar, zwitterionic transition states, accompanied by a significant shifting of the base mispairs toward DNA minor or major grooves. These tautomeric transitions are characterized by a change in

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“…Shortly after the establishment of the spatial organization of the DNA molecule by James Watson and Francis Crick (Watson and Crick, 1953a , b ), the tautomeric hypothesis was formulated (Watson and Crick, 1953b ; Crick and Watson, 1954 ), which considers the transformation or transition of the nucleotide bases from the main (canonical) into the rare (mutagenic) tautomeric form as the main source of the origin of spontaneous point mutations. Since that time, the topic of tautomerism has remained active over the decades to the present day (Löwdin, 1963 , 1966 ; Topal and Fresco, 1976 ; Florian et al, 1994 ; Gorb et al, 2004 ; Brovarets' et al, 2014 ; Godbeer et al, 2015 ; Turaeva and Brown-Kennerly, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

A Quantum-Mechanical Looking Behind the Scene of the Classic G·C Nucleobase Pairs Tautomerization

2020

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For the first time, at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory, a comprehensive quantum-mechanical investigation of the physico-chemical mechanism of the tautomeric wobblization of the four biologically-important G·C nucleobase pairs by the participation of the monomers in rare, in particular mutagenic, tautomeric forms (marked with an asterisk) was provided. These novel tautomeric transformations (wobblization or shifting of the bases within the pair) are intrinsically inherent properties of the G·C nucleobase pairs. In this study, we have obtained intriguing results, lying far beyond the existing representations. Thus, it was shown that Löwdin's G*·C*(WC) base pair does not tautomerize according to the wobblization mechanism. Tautomeric wobblization of the G*·C*(rWC) (relative Gibbs free energy ΔG = 0.00/relative electronic energy ΔE = 0.00 kcal·mol−1) (“r”—means the configuration of the base pair in reverse position; “WC”—the classic Watson-Crick configuration) and G*t·C*(H) (ΔG = −0.19/ΔE = 0.29 kcal·mol−1) (“H”—Hoogsteen configuration;”t” denotes the O6H hydroxyl group in the trans position) base pairs are preceded by the stages of the base pairs tautomerization by the single proton transfer (SPT). It was established that the G*t·C*(rH) (ΔG = 2.21/ΔE = 2.81 kcal·mol−1) base pair can be wobbled through two different pathways via the traditional one-stage mechanism through the TSs, which are tight G+·C− ion pairs, stabilized by the participation of only two intermolecular H-bonds. It was found out that the G·C base pair is most likely incorporated into the DNA/RNA double helix with parallel strands in the G*·C*(rWC), G·C*(rwwc), and G*·C(rwwc) (“w”—wobble configuration of the pair) tautomeric forms, which are in rapid tautomeric equilibrium with each other. It was proven that the G*·C*(rWC) nucleobase pair is also in rapid tautomeric equilibrium with the eight tautomeric forms of the so-called Levitt base pair. It was revealed that a few cases of tautomerization via the DPT of the nucleobase pairs by the participation of the C8H group of the guanine had occurred. The biological role of the obtained results was also made apparent.

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Marcus model of spontaneous point mutation in DNA

Cited by 19 publications

References 35 publications

The Role of Proton Transfer on Mutations

The Role of Proton Transfer on Mutations

Renaissance of the Tautomeric Hypothesis of the Spontaneous Point Mutations in DNA: New Ideas and Computational Approaches

A Quantum-Mechanical Looking Behind the Scene of the Classic G·C Nucleobase Pairs Tautomerization

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