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Making new cells - DNA damage and repair

DNA damage and repairDNA is the genetic ‘instruction manual’ found in all our cells. If DNA becomes damaged, and is not repaired properly, then the cell may get the wrong instructions and start to multiply out of control. This can lead to cancer.

Cancer Research UK scientists have played a major role in this important field of research - discovering how DNA is damaged, how damage is detected and repaired by cells, and how mistakes in this process can lead to cancer. 

We have funded - and continue to fund - a number of the world’s leading researchers working in this area, including Professor Sir David Lane, Dr Tomas Lindahl, Dr Steve West and Professor Steve Jackson to name just a few.

What causes DNA damage?

Our DNA is under constant bombardment, so it is vital that any damage is detected quickly and repaired.

DNA can be damaged by many things – from ultraviolet (UV) radiation in sunlight to chemicals in our environment such as those found in tobacco smoke. Another major cause of damage is the chemical reactions that take place naturally all the time in our cells.

We issued our first warning about the dangers of UV radiation back in 1935. And we have led groundbreaking research into the effects of smoking, as well as influencing governments in the UK and around the world on tobacco control.

We have funded the work of Professor David Phillips for more than ten years. His work is revealing how different chemicals cause damage to DNA, so we can work towards preventing more cases of the disease.

Alerting the cell to damage

Once a cell’s DNA is damaged, it is vital that it is recognised and repaired. Cancer Research UK scientists have discovered a number of crucial 'damage sensors’.

Arguably the most important of these is a protein called p53, which was discovered by Professor David Lane, now our Chief Scientist. Known as the “guardian of the genome”, p53 alerts cells to the presence of DNA damage. This enables them to repair the damage, or causes them to die if the damage is too severe. But the p53 response is inactivated or faulty in most cancers.

Watch a video of Professor Lane talking about the discovery of p53:

Professor Lane and his team continue to break new ground in understanding p53, paving the way for future cancer treatments.

Cancer Research UK scientists in Dundee have identified molecules, called Tenovins, that can re-activate p53 and slow down the growth of tumours. They hope to take these forward into clinical trials in people with cancer.

Professor Steve Jackson is one of the world’s leading lights on DNA damage and repair, particularly focusing on how cells are alerted to DNA damage. He has played a vital role in discovering many of the proteins involved, and finding ways to target them.

Researchers are now working to develop drugs to block these molecular sensors. Because radiotherapy and some types of chemotherapy work by causing excessive damage to DNA in cancer cells so they die, such drugs could make these treatments more effective.

Carrying out repairs

Once damage has been detected, it must be repaired. There are several types of DNA damage, and they all need to be repaired in different ways.

For example, proteins called BRCA1 and BRCA2 are involved in repairing complete breaks in DNA strands. Cancer Research UK-funded scientists played a vital role in discovering that inherited faults in these genes are linked to a high risk of breast and ovarian cancer.

Our scientists are currently testing a drug that blocks the activity of PARP, a crucial part of the cell's DNA 'repair kit'. Developed with the help of Cancer Research UK funding, PARP inhibitors were originally designed to target breast, ovarian or prostate cancer in people with faults in their BRCA1 or BRCA2 genes. But researchers now think they might be suitable for treating a wider range of patients.

Early clinical trial results of PARP inhibitors are very promising. Researchers are now investigating whether the drugs could also be used to treat patients with other genetic faults.

At our London Research Institute, Dr Simon Boulton is studying exactly how BRCA1, BRCA2 and other genes repair DNA, and how this process goes wrong in cancer.

Shapes and structures

p97 proteinMany important advances in cancer biology have been made by structural biologists - researchers who use X-rays and other techniques to discover the three-dimensional structure of proteins or other molecules. By revealing the shapes of important molecules involved in cancer, scientists can design more effective anti-cancer drugs that activate or block them.

For example, Cancer Research UK has funded the work of Professor Laurence Pearl since the early 1990s. His discoveries have revealed how the cell identifies different types of DNA damage, helping to explain why this doesn’t happen properly in cancer cells.

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