Cancer Research UK scientists have identified a long sought after enzyme that plays a critical role in a DNA repair pathway linked with inheritable breast and ovarian cancer, reveals research published in Nature* today (Wednesday).

Familial breast cancers, such as those caused by mutation of the BRCA2 tumour suppressor, are caused by defects in a pathway that rejoins breaks in the DNA.

After an 18-year search, scientists have found a new factor – known as GEN1 – that plays a crucial role in this pathway, and it is likely that this factor may be important for preventing cancer.

This finding expands our understanding of how inheritable breast cancers develop and it is possible that mutations in GEN1 may also be linked with other types of cancer.

Professor Stephen West, based at Cancer Research UK’s Clare Hall laboratories, part of the London Research Institute, said: “This is an important enzyme that plays a key role in cellular reactions that repair damaged DNA. Our finding that this enzyme acts in the same pathway as BRCA2 suggests that it is going to be important for cancer prevention.”

Breaks in DNA are repaired by a process known as recombinational repair, which is regulated by BRCA2. During this process, the broken DNA joins with a DNA template to form a four-way DNA junction.

The GEN1 enzyme found in this study acts as a pair of ‘scissors’ that cuts the four-way junction – a reaction that is essential for forming normal DNA. Loss of this enzyme is thought to lead to genetic damage that can result in cancerous tumours forming.

It is hoped that this discovery will enable scientists to find other genes involved in this repair process that, when damaged or mutated, cause cancer.

Professor West continued: “This discovery adds another piece in the puzzle to improve our understanding of the molecular processes that can lead to cancer. Future studies of GEN1 will provide new insights into these reactions, and provide a more complete picture of the steps that lead to the disease.”

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “Knowing that this enzyme is important for DNA repair is an important step forward in cancer research. Most cancer genes are identified by studying the genetic profile of people affected by the disease. This discovery will allow us to work from the bottom up – genes such as GEN1 will almost certainly determine your risk of cancer.”


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* Identification of Holliday junction resolvases from humans and yeast. Ip et al. Nature, Wednesday 19 November, 2008. doi:10.1038/nature07470.

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