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Deamination features of 5-hydroxymethylcytosine, a radical and enzymatic DNA oxidation product

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Abstract

The 5-methylcytosine derivative 5-hydroxymethylcytosine (5hmCyt), which is generated via enzymatic oxidation, is sometimes referred to as the sixth nucleobase due to its widespread presence in the DNA of brain and embryonic stem cells. In this study, we used density functional based methods and reactivity indices from conceptual DFT to explore the mechanism and key features of the hydrolytic deamination of 5hmCyt. The data obtained are used to compare and contrast this deamination reaction with those of other cytosine derivatives. The deamination process for 5hmCyt is similar to the corresponding processes for other unsaturated derivatives in that the amino form is the reactive one and water addition is the rate-limiting step. However, several differences due to the rotameric asymmetry of the current system are also noted.

Exploration of the spontaneous deamination of 5-hydroxymethylcytosine using computational chemistry

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Acknowledgments

The Faculty of Science at the University of Gothenburg and the Swedish Science Research Council (VR) are gratefully acknowledged for financial support [LAE]. AG and CM thank INSERM for financial support. The research benefited from the support of Aviesan ITMO Cancer within the “Cancer Plan 2009–2013” and the application of Action 3.3. AG furthermore acknowledges support from the Universidad Autonoma de Chile.

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Authors and Affiliations

  1. Laboratoire “Lésions des Acides Nucléiques”, INAC/SCIB - UMR-E n°3 CEA-UJF, CEA Grenoble, 17 avenue des Martyrs, 38054, Grenoble cedex 9, France

    André Grand & Jean Cadet

  2. Investigador Associado Facultad de Cs. De la Salud, Universitad Autonoma de Chile, Carlos Antunez, Providencia, Santiago, Chile

    André Grand

  3. Área Fisicoquímica, Facultad de Ciencias Exactas y Naturales y Agrimensura, UNNE, Campus Universitario, Av. Libertad 5400, 3400, Corrientes, Argentina

    Nelly Jorge

  4. Université de Lyon1, ISA/Laboratoire des Sciences Analytiques UMR 5180, 5 avenue de la Doua, 69622, Villeurbanne Cedex, France

    Christophe Morell

  5. Department of Chemistry and Molecular Biology, University of Gothenburg, 412 96, Göteborg, Sweden

    Leif A. Eriksson

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  1. André Grand
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  2. Nelly Jorge
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  5. Leif A. Eriksson
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Correspondence to Leif A. Eriksson.

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This paper belongs to Topical Collection QUITEL 2013.

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Grand, A., Jorge, N., Morell, C. et al. Deamination features of 5-hydroxymethylcytosine, a radical and enzymatic DNA oxidation product. J Mol Model 20, 2290 (2014). https://doi.org/10.1007/s00894-014-2290-9

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