Carbon-14 decay as a source of non-canonical bases in DNA
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Background: Significant experimental effort has been applied to study radioactive beta-decay in biological systems. Atomic-scale knowledge of this transmutation process is lacking due to the absence of computer simulations. Carbon-14 is an important beta-emitter, being ubiquitous in the environment and an intrinsic part of the genetic code. Over a lifetime, around 50 billion 14C decays occur within human DNA. Methods: We apply ab initio molecular dynamics to quantify 14C-induced bond rupture in a variety of organic molecules, including DNA base pairs. Results: We show that double bonds and ring structures confer radiation resistance. These features, present in the canonical bases of the DNA, enhance their resistance to 14C-induced bond-breaking. In contrast, the sugar group of the DNA and RNA backbone is vulnerable to single-strand breaking. We also show that Carbon-14 decay provides a mechanism for creating mutagenic wobble-type mispairs. Conclusions: The observation that DNA has a resistance to natural radioactivity has not previously been recognized. We show that 14C decay can be a source for generating non-canonical bases. General significance: Our findings raise questions such as how the genetic apparatus deals with the appearance of an extra nitrogen in the canonical bases. It is not obvious whether or not the DNA repair mechanism detects this modification nor how DNA replication is affected by a non-canonical nucleobase. Accordingly, 14C may prove to be a source of genetic alteration that is impossible to avoid due to the universal presence of radiocarbon in the environment.
NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta, Vol. 1840, No. 1 (2014). DOI: 10.1016/j.bbagen.2013.10.003
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