Findings reveals 'limpet-like' proteins can play a key role in DNA repair

Cancer Research UKJan 6 2010

UK scientists have found that a crafty family of 'limpet-like' proteins can play a crucial role in repairing DNA damage - according to two research papers published in Nature today (Wednesday). These findings could pave the way to the design of new anti-cancer drugs which target this process.

Two teams, funded by Cancer Research UK and Breast Cancer Campaign, studied the ways in which cells respond to DNA damage. Failure to repair this damage accurately can lead to cell death and trigger diseases such as cancer.

Both studies independently found that a family of Small Ubiquitin-like Modifier (SUMO) proteins could track down sites in the body where DNA damage has occurred, attach themselves to normal proteins, and guide them in fixing the genetic faults. These proteins could unlock a secret to the body's cancer fighting mechanisms.

It is hoped that this new knowledge may help scientists to develop drugs which work with common cancer treatments, such as chemotherapy and radiotherapy, to kill cancerous cells and allow the body to reproduce healthy new ones. The scientists made this discovery by observing the way cancer cells behave in the laboratory.

Professor Steve Jackson, who led the first study and who is senior group leader at the Cancer Research UK/Wellcome Trust Gurdon Institute at the University of Cambridge, said: "What's really striking about our discovery is the capacity these SUMO proteins have to locate and help repair DNA damage as it occurs. They can also recruit other proteins to help repair double strand DNA breaks - the most severe type of DNA damage of all. We found these proteins can strengthen the cells' defences against DNA damage. When their work is done, the SUMO proteins then detach themselves and move on - which is quite incredible."

The second study was led by Dr Jo Morris, a Breast Cancer Campaign fellow in the Cancer Genetics Laboratory at Kings College London. This team looked specifically at the role of SUMO in relation to the breast cancer gene BRCA1 - which, when faulty, is associated with a very high risk of breast cancer.

Dr Morris said: "Our findings showed that after DNA damage, SUMO becomes attached to BRCA1, switching it on and helping prevent breast cancer forming.

"We discovered how the cells in our body co-ordinate the difficult task of repairing potentially breast cancer causing DNA breaks and how they direct BRCA1 to do its job to stop tumours forming.

"This new insight is the first step towards developing drugs which may protect normal cells from the side effects of chemotherapy, or improve the effectiveness of current breast cancer treatments."

Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "DNA damage, particularly double strand DNA breaks, are a fundamental cause of cancer and we know that people who have mutations in the BRCA1 gene have a higher risk of developing some kinds of cancer. Discovering that these 'limpet like' proteins play such an important role in repair may provide new opportunities to stop cancer from growing.

"But this is an extremely complex and intricate biological process so it may be many years before we can use this knowledge to safely intervene and help treat cancer patients."