Understanding the Mechanism of DNA Repair

  • ChemPubSoc Europe Logo
  • Author: Sarah Millar
  • Published Date: 28 December 2013
  • Source / Publisher: Chemistry – A European Journal/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
thumbnail image: Understanding the Mechanism of DNA Repair

Related Societies

Nonheme iron dioxygenases catalyze a range of important reactions in nature. For example, AlkB repair enzymes catalyze the demethylation of alkylated DNA bases in humans, a vital reaction in the body that heals externally damaged DNA bases. However, there are many unanswered questions related to the activity of nonheme iron dioxygenases and the catalytic transformation of substrates.

Sam P. de Visser, University of Manchester, UK, and colleagues have performed a quantum mechanics/molecular mechanics (QQ/MM) study on the demethylation of the N1-methyladenine fragment by AlkB repair enzymes. They identified only one feasible oxygen-binding site in the enzyme. This site was on the iron center trans to His131. The iron(III)–superoxo species is separated from the substrate by a considerable distance and its approach is blocked by an Arg residue. This prevents the iron(III)–superoxo from reacting with substrate.

However, the team discovered that the catalytically active iron(IV)–oxo intermediate can undergo isomerization assisted by the Arg residue in the substrate binding pocket. This isomerization brings the oxo group in close contact with the methyl group of the alkylated DNA base. This enables a subsequent rate-determining hydrogen-atom abstraction to form a radical intermediate followed by rebinding to give alcohol products.

These findings show that it is essential to separate the substrate- and oxygen-binding channels, otherwise the iron(III)–superoxo will react with substrate and prevent the repair reaction of the DNA.

Article Views: 2899

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter

A product of ChemPubSoc Europe (16 European Chemical Societies)and Wiley-VCH