Science breakthrough explains how cells repair broken DNA

Scientists have identified crucial elements necessary for repairing damaged DNA – the blueprint for all living cells.

The breakthrough will further our understanding of how diseases that are associated with DNA instability, such as cancer, arise. The findings also point to how new drug therapies could be developed for treating cancer.

Dr Aidan Doherty, a reader in biochemistry at the University of Sussex’s Genome Damage and Stability Centre, led a collaboration of scientists at Sussex and in the USA and found that the process of repairing DNA breaks was much simpler than previously thought. By manipulating synthetic DNA breaks, his team showed that two proteins, Ku and Ligase, commonly found in bacteria, acted together to identify and repair these breaks.

Close relatives of these proteins are found in the cells of other living organisms, including humans and yeast. When researchers experimented on yeast cells lacking these proteins, they found that the bacterial proteins alone could repair the yeast cells’ DNA. These findings suggest that there is a common repair process that has been conserved throughout evolution from bacteria to humans.

“These findings have important implications for our understanding of repair mechanisms in human cells, “ says Dr Doherty. “Our DNA can be damaged by any number of things, from sunlight to oxygen. This happens continuously and most of the time our cells repair themselves correctly. But occasionally inaccurate repair of these breaks occurs and this has the potential to contribute to cell mutation, allowing genetic material to be lost, which can lead to DNA instability and ultimately cancer.

“Now that we have identified the essential protein activities necessary for this repair process, we can begin to understand how cells repair DNA breaks. There is a great deal of interest in designing drugs that target related repair systems in human cells to inhibit the growth of cancerous cells and we are likely to see new cancer therapies, based on these inhibitors, appearing in the next five to ten years.”

The work has recently been patented and is currently being developed as a research tool for the research and biotechnology communities.

Dr Doherty’s team carried out the research with scientists at the Michigan Medical School and University of Maryland School of Medicine. Financial support came from the Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Royal Society.

A paper, entitled “Mycobacterial Ku and Ligase proteins constitute a two-component NHEJ repair machine,” was published in Science journal on October 21, 2004.