Nobel Prizes for DNA repair scientists
Today (10th December 2015) the Nobel Prizes for Chemistry are 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.
How is DNA damaged?
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 and cigarette smoke. Free radicals produced by the air that we breathe also causes damage or accidental errors can be introduced just through 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’. This is where an error occurs in the DNA, much like a typo in a book. Machinery comes along, cuts out the incorrect letter and replaces it with the correct letter.
The second prize winner 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. If you think of DNA as a ladder, nucleotide excision repair occurs where there is a fault with one of the rungs of the ladder. In order to correct the rung, the machinery removes a big chunk off one side of the ladder before building the rung and side correctly.
The third 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. This machinery detects and corrects mismatched errors, like if one half of a zip didn’t match the other side it would not zip up properly. 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.
Worldwide Cancer Research plays its part
Over the last 35 years we have funded a vast number of DNA damage projects. For example, 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. It is 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 Professor John Rouse, Dr Libor Macurek or Professor Andrés Aguilera could be on the Nobel Prize list in years to come?