News Release

Surprising new insights into the repair strategies of DNA

Peer-Reviewed Publication

University of Nottingham

A microscopic single-celled organism, adapted to survive in some of the harshest environments on earth, could help scientists gain a better understanding of how cancer cells behave.

Experts at The University of Nottingham were astonished to discover that the archaeon Haloferax volcanii was better at repairing DNA damage if enzymes, that are widely considered to be critically important in coordinating the repair of DNA, were mutated.

Dr Thorsten Allers, from the Institute of Genetics, said: "These results surprised us. It is the first time, as far as we know, that anybody has found such resistance to DNA damage in mutant cells. Normally, cells that are missing enzymes for DNA repair become more sensitive to DNA damage."

Like cancer cells, archaea are polyploid — which means they contain more than two sets of chromosomes. Although similar in structure and appearance to bacteria, archaea share a common ancestor with eukaryotes, which include plant and animals. This kinship is at its closest in the way archaea process DNA. Although Dr Allers's discovery is at the basic biological level, it is the similarities with cancer cells that make him convinced that scientists have much more to learn from archaea.

Discovered just 32 years ago, there are less then 200 experts around the world studying archaea. On the other hand, the mechanisms by which cells perform the repair of DNA breaks has been the subject of decades of research using bacterial and eukaryotic cells. We are only just beginning to learn how this process works in archaea.

DNA breaks can be caused by, among other things, radiation, UV rays and chemotherapy. Dr Allers said: "All organisms can use enzymes to simply glue the broken strands of DNA back together, but this is prone to error and can give rise to mutations which cause cancer. The alternative is to perform a kind of molecular gymnastics called recombination, where healthy strands of matching DNA are used to repair the broken ends. This is a complicated and time-consuming strategy to mend DNA, but avoids mutations. When the enzymes that carry out recombination are defective, cancer can develop more easily. This is what happens in patients with mutations in the BRCA breast cancer genes."

Dr Allers's research, published in the journal PLoS Genetics, shows how, unlike other organisms, Haloferax volcanii deliberately avoids using recombination to repair DNA breaks. His results suggest that other polyploid organisms, such as cancer cells, might work in much the same way. What scientists need to know now is why.

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Notes to editors: The University of Nottingham is ranked in the UK's Top 10 and the World's Top 100 universities by the Shanghai Jiao Tong (SJTU) and Times Higher (THE) World University Rankings.

More than 90 per cent of research at The University of Nottingham is of international quality, according to RAE 2008, with almost 60 per cent of all research defined as 'world-leading' or 'internationally excellent'. Research Fortnight analysis of RAE 2008 ranks the University 7th in the UK by research power. In 27 subject areas, the University features in the UK Top Ten, with 14 of those in the Top Five.

The University provides innovative and top quality teaching, undertakes world-changing research, and attracts talented staff and students from 150 nations. Described by The Times as Britain's "only truly global university", it has invested continuously in award-winning campuses in the United Kingdom, China and Malaysia. Twice since 2003 its research and teaching academics have won Nobel Prizes. The University has won the Queen's Award for Enterprise in both 2006 (International Trade) and 2007 (Innovation — School of Pharmacy), and was named 'Entrepreneurial University of the Year' at the Times Higher Education Awards 2008.

Nottingham was designated as a Science City in 2005 in recognition of its rich scientific heritage, industrial base and role as a leading research centre. Nottingham has since embarked on a wide range of business, property, knowledge transfer and educational initiatives (www.science-city.co.uk) in order to build on its growing reputation as an international centre of scientific excellence. The University of Nottingham is a partner in Nottingham: the Science City.

Story Credits

More information is available from Dr Thorsten Allers on +44 (0)115 823 0304, thorsten.allers@nottingham.ac.uk or Lindsay Brooke - Media Relations Manager on +44 (0)115 951 5751, lindsay.brooke@nottingham.ac.uk


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