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An Electronic Clue In The Mystery of DNA Repair

DNA repair machines may home in on the electrical signals created by mutations

Here’s a curious puzzle involving DNA molecules. DNA is regularly damaged by ordinary wear and tear and the constant buffeting of ionising radiation. However, cells possess an extraordinary collection of molecular machines such as repair enzymes that rapidly identify the defects and repair them.

The puzzle is how they do it. One idea is that repair enzymes simply float about for long enough and eventually find damaged regions. But the numbers just don’t stack up. Genes are usually between 1000 and 1,000,000 base pairs long. By contrast, a typical mutation usually involves just a handful of base pairs. That’s just too small to find using a random walk with any reliability. Some other form of active location finding must be going on.

One theory is that mutations change the electrical characteristics of a stretch of DNA and that this creates a signal that repair enzymes can home in on, like electricians locating a break in a circuit. The trouble is that DNA doesn’t conduct electricity like a power cable and so it isn’t clear how this would work.

Now Arkady Krokhin at the University of North Texas and few buddies have worked out how DNA may do it. The key turns out to be that different regions of DNA have different electrical characteristics. The group has calculated from first principles the way in which charge flows in different regions. They say that in exons–the information carrying parts of genes–the energy spectrum of the molecule allows delocalised electrons to exist. In these areas, charge can flow.

However the energy spectrum of the regions that do not carry information–the introns–does not allow for delocalised electrons. So introns are effectively insulators.

That sets up well defined regions within DNA that can be identified electronically.It also means that any change in electronic properties caused by a mutation would be largely confined too. That immediately suggests a way that repair enzymes can home in on damage.

Of course, this work is just one step towards a coherent theory that explains DNA repair (which actually involves many different processes).

But the beauty of this approach is that it could also explain why some damage goes unrepaired, leading to cell death and even cancer.

The thinking is that certain mutations cause less of an electrical change than others. These mutations are “electronically masked” and so go undetected by repair enzymes. There is even experimental evidence for this from resistance measurements done on DNA with cancer-causing mutations.

If this theory is true, one important question is how might it be possible to exploit DNA’s electrical characteristics to detect and even prevent cancer in future?

Ref: arxiv.org/abs/0911.2953: Inhomogeneous DNA: Conducting Exons And Insulating Introns

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