Role of BRCA1 in DNA repair unravelled

Scientists at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, have shed light on the way DNA is repaired in cells. They have found that a protein called CtIP interacts with the BRCA1 gene, directing cells to mend breaks in DNA accurately. Mutations in the BRCA1 gene are known to increase a woman's risk of developing breast cancer by up to 85 per cent, so the findings have implications for the development of new treatments for breast cancer. The results are published in the 21 May issue of the journal Nature.

The researchers used chicken cells to study DNA repair mechanisms. They found that DNA breaks occur in the cells all the time, due to the 'wear and tear' of cell division. If breaks are not repaired accurately, cells are more likely to become cancerous. Until now, scientists didn't know why mutations in BRCA1 increased cancer risk. By studying DNA repair mechanisms in chicken cells, they found that a protein - known as CtlP - is essential for repairing the DNA breaks that occur naturally during cell division. But when the BRCA1 gene is mutated, it doesn't interact with the CtlP protein in the normal way, forcing the cell to use a less accurate method of DNA repair which simply 'sticks' the two ends of the broken DNA strand back together rather than replacing the missing DNA. This can lead to inaccuracies in the genetic code which sometimes trigger the cell to become cancerous.

Dr Kevin Hiom, who led the study, explained: 'If you are lacking BRCA1 you cannot repair DNA accurately'. He believes the research may open up new treatment avenues: 'Our findings help us to understand how breaks in DNA strands can be repaired in a way that preserves our genetic code so that harmful mutations, which may lead to cancer, are kept to a minimum. By promoting the interaction of BRCA1 with CtIP it might be possible to promote the accuracy of DNA repair - even in people with a faulty gene'.

Ed Yong, information manager at Cancer Research UK, explained the importance of CtIP in cell repair: 'our cells have two major ways of repairing broken DNA and this study shows that the CtIP protein is a switch that flicks between them'. He added: 'In doing so, the protein helps our cells to mend damaged DNA and fix the sorts of faults that could eventually lead to cancer. It's one of a number of molecular guardians that keep watch over the integrity of our genes.'

About 11 per cent of women will develop breast cancer in their lifetimes and about 5 per cent of these cases are triggered by a mutation in their BRCA1 gene.