Scientists find DNA repair 'accuracy switch'

In collaboration with the Press Association

UK scientists have shed light on how our cells use two different methods to repair damaged DNA, and how they switch between them.

One pathway involves the BRCA1 'breast cancer gene', so deepens scientists' understanding of how cancer develops and could one day lead to new treatments for the disease.

Researchers at the Medical Research Council Laboratory of Molecular Biology in Cambridge studied cells taken from chickens, whose DNA repair mechanisms are similar to those found in humans.

Cells have two main DNA repair pathways that were thought to function at different stages of a cell's life cycle and protect against cancer-causing DNA damage.

One mechanism, called 'homologous recombination', is much more accurate than the other, known as 'end joining'.

But how the cell activates the more accurate pathway when it gets ready to divide was unknown.

The Cambridge team's latest results suggest that a protein called CtIP is the master switch that flips the cell between the two pathways.

When CtIP becomes activated, say the scientists, it causes the protein made by the BRCA1 gene to bind to the damaged DNA.

This in turn activates the highly accurate homologous repair pathway, so that errors are minimised when the cell divides, and protecting against cancer.

Lead author Dr Kevin Hiom, whose findings are published in the journal Nature, commented: "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.

"Up to now, it was unclear how this accurate mechanism for repairing DNA breaks is turned on so we are very pleased with the result," Dr Hiom added.

Ed Yong, Cancer Research UK's health information manager, revealed: "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.

"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."

Mr Yong noted: "It is too early to say if this work could go on to benefit people affected by cancer, but understanding the basic biology of cancer has always played a central role in efforts to beat the disease."

References

Yun, M., & Hiom, K. (2009). CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle Nature, 459 (7245), 460-463 DOI: 10.1038/nature07955