title: Deamination features of 5-hydroxymethylcytosine, a radical and enzymatic DNA oxidation product.
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.
authors.affiliation: Laboratoire "Lésions des Acides Nucléiques", INAC/SCIB - UMR-E n°3 CEA-UJF, CEA Grenoble, 17 avenue des Martyrs, 38054, Grenoble cedex 9, France.
authors.forename: André
authors.initials: A
authors.lastname: Grand
authors.forename: Nelly
authors.initials: N
authors.lastname: Jorge
authors.forename: Christophe
authors.initials: C
authors.lastname: Morell
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D003198:Computer Simulation; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003641:Deamination; D004735:Energy Transfer; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA