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Highlights in Chemical Biology

Chemical biology news from across RSC Publishing.

Discovering the secrets of DNA repair

18 August 2008

A modified DNA is helping scientists to understand the sophisticated DNA repair mechanisms that allow dormant bacteria to come 'back to life'.

Thomas Carell and Eva Bürckstümmer at the Ludwig Maximilian University of Munich, Germany, have made short DNA strands containing lesions. Carell explains that this is the key to understanding DNA repair. 'So far any study of this enigmatic process has been hampered by a lack of DNA containing this lesion,' he explains.

"The lesions are analogues of those triggered when UV light acts on DNA stored in spores such as the Bacillus bacteria spore"
The lesions are analogues of those triggered when UV light acts on DNA stored in spores such as the Bacillus bacteria spore. In nature, these spores can lie dormant for many years, storing DNA, but then return to life, explains Carell. How spores store DNA and how lesion repair occurs are the questions the German duo would like to answer.

Carell and Bürckstümmer made their DNA strands by synthesising two isomers of a dinucleotide lesion analogue and incorporating them into DNA. They found that one DNA was more stable than the other, suggesting that the natural lesion could have a similar structure to the analogue in the more stable DNA. Carell points out that similar lesion analogues are substrates for the spore DNA repair enzyme so that the new strands could help further studies into the enzyme mechanism. 

Cartoon of DNA repair

Glen Burley, an expert in DNA nanotechnology at the University of Leicester, UK, says that the work is exciting because it provides a method for investigating how bacterial spores repair damaged DNA. 'This is a compelling question as DNA damage processes in spores differ from those in mammals,' he says. 'These methods would likely lead to a greater understanding of how spores can survive for long periods and in hostile conditions - for example hot springs or under UV light exposure.'

"Such enzymes are also operating in our cells, so a deeper understanding of this class of enigmatic enzymes is desperately needed"
- Thomas Carell
Carell explains that although the repair process in the spore is unique, the phenomenon of lesion recognition by enzymes is more general. 'Such enzymes are also operating in our cells,' he says, 'so a deeper understanding of this class of enigmatic enzymes is desperately needed.' Carell adds that he is particularly interested in learning more about failures in the repair process. 'These are responsible for mutations which in turn lead to dangerous cellular situations which might produce cancer,' he says. 

Katherine Davies

Link to journal article

Synthesis and properties of DNA containing a spore photoproduct analog
Eva Bürckstümmer and Thomas Carell, Chem. Commun., 2008, 4037
DOI: 10.1039/b810008j

Also of interest

The spore photoproduct lyase repairs the 5S- and not the 5R-configured spore photoproduct DNA lesion
Marcus G. Friedel, Olivier Berteau, J. Carsten Pieck, Mohamed Atta, Sandrine Ollagnier-de-Choudens, Marc Fontecave and Thomas Carell, Chem. Commun., 2006, 445
DOI: 10.1039/b514103f

Processing of DNA damage clusters in human cells: current status of knowledge
Alexandros G. Georgakilas, Mol. BioSyst., 2008, 4, 30
DOI: 10.1039/b713178j