University of Dundee

DNA 'Swiss army knife' discovered by Dundee scientists

13 Jul 2009

DNA 'Swiss army knife' discovered by Dundee scientists

Scientists in the Medical Research Council (MRC) Protein Phosphorylation Unit at the University of Dundee have discovered a group of proteins acting like a 'Swiss Army Knife' to repair damaged DNA in our cells, a finding which could have future implications for cancer treatments.

Dr John Rouse and colleagues in the MRC Unit, which is based in the College of Life Sciences at Dundee discovered a set of proteins, known as 'SLX' proteins, which are present in each cell and play a vital role in maintaining healthy DNA and thus preventing mutations which can lead to cancers.

'The DNA in every cell of the human body encodes the instructions for the correct working of the each cell,' said Dr Rouse, a Programme Leader in the Medical Research Council Protein Phosphorylation Unit in the College of Life Sciences.

'A major problem is that DNA becomes damaged regularly. If DNA damage is not fixed quickly then the instructions for the proper functioning of the cell are altered and the result is mutations that can cause the cell to become abnormal. This is essentially what causes cancer.'

'However, cells are very good at recognising when DNA has become damaged and they start to repair the damage. For example, cells can quickly detect breakages in DNA and quickly fix these breaks. Many different factors help this process but we still haven’t identified all of them or exactly how this process works.'

'With our findings we have unlocked a major part of the puzzle. We discovered a new set of proteins - the 'SLX' proteins - that are essential for the repair of DNA breaks.'

'Together these proteins act like a Swiss Army knife or a 'molecular toolkit' for DNA repair. During repair of DNA breaks, DNA 'branchpoints' (known as Holliday junctions) and DNA 'flaps' are produced that must be cut for repair to be completed. Scientists have been hunting for the factors that can cut Holliday junctions in human cells for more than two decades - our study shows that these DNA branchpoints are cut by the SLX proteins. Cells that do not have the SLX proteins are unable to repair DNA breaks and their DNA becomes irreversibly damaged and die. This underlines the fundamental importance of the SLX proteins.'

'Now that we have identified these proteins and the role they play in repairing DNA we can start to develop drugs that target these processes. This could have a significant effect in cancer, primarily in helping to greatly enhance the efficacy of drugs used in chemotherapy treatments.'

Dr Rouse’s team worked closely on the research with the laboratory of Professor David Lilley, also based in the College of Life Sciences at Dundee, who is a world-renowned expert in Holliday junctions.

The research is published in the latest edition of the journal Molecular Cell.

The work was funded by the Medical Research Council and St Andrews-based charity AICR (Association For International Cancer Research).

Dr Mark Matfield, from AICR, said, 'This is an important step forward in our basic understanding of DNA repair. Since damage to DNA is, ultimately, the cause of all cancers, we really want to understand how cells can repair it. These findings could have implications for future developments in both cancer prevention and treatment.'

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