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Nobel Prize for DNA repair scientists

Today (10th December 2015) the Nobel Prize in Chemistry is awarded.  Three eminent scientists will be acknowledged for their game-changing discoveries about how cells repair damage to their DNA – a vital process in preventing cancer.

We have millions of cells in our bodies. Each cell deals with thousands of injuries to their DNA every single day.  This is because our DNA is constantly under attack by things ranging from UV in sunlight, cigarette smoke, free radicals produced by the air that we breathe or just through accidental errors during the DNA copying process.

Having ways to monitor, detect and repair this damage is vital to prevent cells becoming cancerous.  Knowledge of how this DNA repair takes place also gives scientists the upper hand against cancer and has aided the development of new cancer treatments.

Nobel prize winner Tomas Lindahl, at the Francis Crick Institute and Clare Hall Laboratory in England, discovered the molecular machinery behind a DNA repair mechanism called ‘base excision repair’.

Sharing the prize is Aziz Sancar at the University of North Carolina in the USA.  His breakthrough was finding the DNA repair mechanism called ‘nucleotide excision repair'.  This is what cells use to repair DNA damaged by the UV in sunlight, amongst other things. In fact, people who have faulty nucleotide excision repair systems often develop skin cancer.

The final Nobel Prize winner is Paul Modrich at the Howard Hughes Medical Institute and Duke University School of Medicine, also in the USA.  He discovered ‘mismatch repair’, a similar process to nucleotide excision repair.  It is most commonly used to repair errors that occur when the DNA is being copied in order to make new cells.  Defects in mismatch repair are known to cause an inherited form of bowel cancer.

Over the last 35 years we have funded a vast number of DNA damage projects. Back in 2009, our funding to Professor John Rouse at the MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee helped them discovered a group of proteins acting like a `Swiss Army Knife’ to repair damaged DNA in our cells which had baffled scientists for over twenty years.

Current research includes that of Dr Libor Macurek at the Institute of Molecular Genetics, Prague, Czech Republic.  Dr Macurek and his team have identified a mutation in a gene called PPM1D which may cause cells to become cancerous.  The fault causes PPM1D to produce a protein which is much shorter than usual. The PPM1D protein is part of the cell ‘checkpoint’ machinery.  Checkpoints make sure cells with damaged DNA are prevented from growing and dividing until the DNA has been repaired. The PPM1D protein’s role is to switch off the checkpoint machinery so the cell can continue growing. But Dr Macurek thinks that the short version of the protein is almost too good at its job, shutting down the checkpoint machinery too soon and before DNA damage has been repaired. This could spell disaster and allow cells to divide without any control so he is investigating it.

Another project is Professor Andrés Aguilera at the University of Seville, Spain. He is studying whether special DNA–like molecules called R-loops could be a marker of tumour cells.  If R-loops are able to accumulate in cells, they become a major source of DNA damage called ‘replication stress’, which is commonly found in cancer cells. He believes R-loops might one day be used as a new diagnostic tool to detect cancer early on, when treatment is more likely to succeed.

Tomas Lindahl, Aziz Sancar and Paul Modrich made ground-breaking discoveries that changed the way the world looked at DNA and DNA damage and they truly deserve their prizes.  But there is still so much we don’t know and so much we need to understand about DNA damage, how cancer begins…..and how cancer can be stopped.  That is why we must keep funding early stage research like this.  Until we find all the answers to cancer, the research must never stop.  Who knows whether Dr Libor Macurek and Professor Andrés Aguilera could be in the Nobel Prize list in years to come?

Further information

We have previously funded several Nobel Laureates including Sir Paul Nurse and Cesar Milstein.  Our former Vice-President, Sir James Black was also a Nobel Laureate.