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Using high-performance computers, the research team from Curtin and Los Alamos National Laboratory were able to show radioactivity could break apart molecular structures which encode genetic information — creating new molecules that do not belong to the four-letter alphabet of DNA.

Naturally occurring radioactivity muddles DNA

Natural radioactivity within DNA can alter chemical compounds, providing a new pathway for genetic mutations.

The Curtin University research, recently published in the journal Biochimica et Biophysica Acta-General Subjects, for the first time looked at natural radioactivity within human DNA on the atomic-scale.

While radioactivity occurs naturally in our bodies as well as in every living organism across the planet, it was never thought to affect our DNA in such a way.

Using high-performance computers, the research team from Curtin and Los Alamos National Labs showed radioactivity breaking apart molecular structures which encode genetic information — creating new molecules that do not belong to the four-letter alphabet of DNA.

Professor Nigel Marks from Curtin’s Discipline of Physics and Astronomy and Curtin’s Nanochemistry Research Institute said the new molecules may well generate mutations by confusing the replication mechanisms in DNA.

“This work takes an entirely new direction on research into natural radioactivity in biology and raises important questions about genetic mutation,” Professor Marks said.

“We have discovered a subtle process that could easily be overlooked by the standard cell repair mechanisms in the body, potentially creating a new pathway for mutations to occur.”

Professor Marks said the work was both exciting and unexpected, emerging as a spin-off from an Australian Research Council funded project on nuclear waste.

“As part of the project between Curtin and Los Alamos we developed a suite of computational tools to examine deliberate radioactivity in crystalline solids, only to later realise that the same methods could be applied to natural radioactivity in molecules,” he said.

“This direction was an unplanned outcome of our research program – just the way blue skies research should be.”

The natural radioactivity in focus involved the decay of carbon atoms, Carbon-14, turning into nitrogen atoms, Nitrogen-14.

Professor Marks adds that this is one of the most abundant forms of radioactive decay occurring in biological systems.

Over a human lifetime, around 50 billion Carbon-14 decays occur within our DNA.

“While it is still not obvious how DNA replication is affected by the presence of chemical compounds that are different to the four-letter alphabet of DNA, it is quite remarkable to consider that Carbon-14 could be a source of genetic mutation that would be impossible to avoid due to the universal presence of radiocarbon in the environment,” Professor Marks added.

Highlights
• We used ab initio methods to quantify 14C decay-induced bond-breaking in DNA.
• Carbon-14 beta-decay is sometimes sufficient to break chemical bonds in DNA.
• Ring structures and double-bonds enhance the molecular resistance to 14C decay.
• Carbon-14 decay provides a mechanism for creating wobble-type mispairs.

Abstract
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.