Carbon-14 decay as a source of non-canonical bases in DNA

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...

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Main Authors: Sassi, Michel, Carter, Damien, Uberuaga, B., Stanek, C., Marks, Nigel
Format: Journal Article
Published: Elsevier BV 2013
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/32103
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author Sassi, Michel
Carter, Damien
Uberuaga, B.
Stanek, C.
Marks, Nigel
author_facet Sassi, Michel
Carter, Damien
Uberuaga, B.
Stanek, C.
Marks, Nigel
author_sort Sassi, Michel
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-321032019-02-19T04:27:56Z Carbon-14 decay as a source of non-canonical bases in DNA Sassi, Michel Carter, Damien Uberuaga, B. Stanek, C. Marks, Nigel Non-canonical base Beta-decay Carbon-14 Bond-breaking DNA Mutation 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. 2013 Journal Article http://hdl.handle.net/20.500.11937/32103 10.1016/j.bbagen.2013.10.003 Elsevier BV fulltext
spellingShingle Non-canonical base
Beta-decay
Carbon-14
Bond-breaking
DNA
Mutation
Sassi, Michel
Carter, Damien
Uberuaga, B.
Stanek, C.
Marks, Nigel
Carbon-14 decay as a source of non-canonical bases in DNA
title Carbon-14 decay as a source of non-canonical bases in DNA
title_full Carbon-14 decay as a source of non-canonical bases in DNA
title_fullStr Carbon-14 decay as a source of non-canonical bases in DNA
title_full_unstemmed Carbon-14 decay as a source of non-canonical bases in DNA
title_short Carbon-14 decay as a source of non-canonical bases in DNA
title_sort carbon-14 decay as a source of non-canonical bases in dna
topic Non-canonical base
Beta-decay
Carbon-14
Bond-breaking
DNA
Mutation
url http://hdl.handle.net/20.500.11937/32103