Research reveals molecular mechanism of DNA repair

New research led by scientists at the University of Essex has given an insight into how the body finds damage in the DNA code to repair it.

From rays of sunlight to harmful tobacco smoke, our bodies are bombarded every single day by a range of environmental toxins which damage our DNA.

Our bodies work hard to find this damage and repair it, but how the damage is found in the first place is one the great unanswered questions in the repair field.

However, new research led by scientists at the University of Essex, has given an insight into how the body finds damage in the DNA code to repair it.

The findings, published in journal Molecular Cell, reveal an important breakthrough in how proteins working together offer a faster, more effective way of finding the damaged DNA.

As lead researcher Dr Neil Kad, from the Department of Biological Sciences, explained, understanding the processes of how the body repairs itself can lead to a greater understanding of cancer and the ageing process, two leading health issues in the UK.

Working in conjunction with researchers Bennett Van Houten at the University of Pittsburgh and David Warshaw at the University of Vermont, USA, scientists at Essex discovered that DNA-repair proteins appear to scan the genome for errors by jumping like fleas between DNA molecules. By tagging the proteins with quantum dots, the researchers were able to watch the proteins at work, trawling around looking for damage which needed repairing.

The researchers tagged two bacterial repair proteins, called UvrA and UvrB, with quantum dots - semi-conductor nanocrystals that light up in different colours - to make it possible to see how they moved. They also stretched the usually clumped DNA into multiple 'tightropes' to see the process more clearly.

They found that the UvrA proteins randomly jumped from one DNA molecule to the next, holding on to one spot for about seven seconds before hopping to another site. But the real breakthrough came when it was discovered that the search for damage became quicker and more efficient when UvrA formed a complex with UvrB molecules (UvrAB). This new, quicker search cut the total time to check the genome from three hours down to just 13 minutes.

'This is the first time we have seen how two different proteins working together change the mechanism of search,' explained Dr Kad

The researchers are now exploring the possibility that the complexes sample the shape or chemical configuration of DNA by interacting with it; an error could alter the local DNA structure, changing its handshake with the repair proteins and perhaps triggering a corrective response.

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