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Aging and disease    2015, Vol. 6 Issue (3) : 216-227     DOI: 10.14336/AD.2014.0924
Review Article |
Mechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer
Afanas’ev Igor()
Vitamin Research Institute, Moscow, Russia, Porto, Portugal
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Superoxide is a precursor of many free radicals and reactive oxygen species (ROS) in biological systems. It has been shown that superoxide regulates major epigenetic processes of DNA methylation, histone methylation, and histone acetylation. We suggested that superoxide, being a radical anion and a strong nucleophile, could participate in DNA methylation and histone methylation and acetylation through mechanism of nucleophilic substitution and free radical abstraction. In nucleophilic reactions superoxide is able to neutralize positive charges of methyl donors S-adenosyl-L-methionine (SAM) and acetyl-coenzyme A (AcCoA) enhancing their nucleophilic capacity or to deprotonate cytosine. In the reversed free radical reactions of demethylation and deacetylation superoxide is formed catalytically by the (Tet) family of dioxygenates and converted into the iron form of hydroxyl radical with subsequent oxidation and final eradication of methyl substituents. Double role of superoxide in these epigenetic processes might be of importance for understanding of ROS effects under physiological and pathological conditions including cancer and aging.

Keywords superoxide      DNA and histone methylation and acetylation      aging      cancer     
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present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 June 2015
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Afanas’ev Igor
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Afanas’ev Igor. Mechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer[J]. Aging and disease, 2015, 6(3): 216-227.
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Figure 1.  Mechanism of DNMT- catalyzed DNA methylation.

A. SAM-dependent methylation of cytosine catalyzed by methyltransferases (DNMT). B. SAM-dependent methylation of lysine catalyzed by lysine methyltransferases (PKMT). C. AcCoA-dependent acetylation of lysine catalyzed by histone acetyltransferases (HAT).

Figure 2.  Free Radical Mechanism of DNA demethylation.

A. Ensymatic complex. B. Superoxide-bound complex. C. The addition of methylcytosine. D. The formation of free radical. E. The formation of hydroxymethylcytosine.

Figure 3.  Hypothetic mechanism of superoxide-dependent DNA methylation.

A. Mechanism of superoxide participation in DNA methylation through the deprotonation of cytosine. B. Mechanism of superoxide participation in DNA methylation through the neutralization of the positive charge of S-adenosyl-L-methionine (SAM).

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