17 October 2007

How cells recognise damage to their DNA

Every cell in the body suffers 10,000 damaging events in its DNA every single day, and probably more if you smoke or sunbathe. DNA is the only material in the cell that is actively repaired, as opposed to throwing it away and making it anew. It is only DNA repair that stops us from contracting cancer on a regular basis. This requires proteins that can recognise and manipulate damaged DNA.

New research from the Universities of Dundee and Leeds, published in the prestigious scientific journal Nature, provides novel insight into how these proteins can recognise structures in DNA that has become damaged or `branched’.

The researchers, including Professor David Lilley FRS at Dundee, studied a particular enzyme - T7 endonuclease 1 - which plays a central role in identifying a branched feature in DNA called a Holliday junction.

Using x-ray crystallography techniques, they were able to build a 3-D picture of the enzyme, giving a much clearer understanding of how it works. This represents a major breakthrough in investigating the fundamental mechanisms at work behind the formation of a person’s DNA and how viruses replicate their DNA in the body.

"This is a big step forward, and provides great new insight into the recognition of branched DNA," said Professor Lilley, Director of the Cancer Research UK Nucleic Acid Structure Research Group at Dundee.

"The new structural knowledge will provide considerable impetus to take this field further."

This work represents the culmination of a long collaboration between teams of scientists, led by Professor Lilley at Dundee and Professor Simon Phillips at Leeds.

The research was funded by Cancer Research UK, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC).

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