Scientists discover 'protector of the genome'

Cancer Research UK

CANCER RESEARCH UK scientists have discovered a crucial protein called RTEL1 that stops cells from becoming vulnerable to developing cancer, according to research published today (Thursday) in Cell*.

Scientists at the charity's London Research Institute Clare Hall Laboratories, have for the first time, shown that RTEL1** plays an important role in protecting our cells from DNA rearrangements arising from incorrect DNA repair events, which can lead to the onset of cancer. These findings could result in the protein becoming a target for future cancer treatments.

Lead author Dr Simon Boulton, head of the London Research Institute's DNA damage response laboratory said: "Studies in yeast have previously identified the Srs2 protein as a critical regulator of DNA repair events essential for maintaining chromosome integrity. Despite 30 years of research an equivalent of Srs2 in humans has remained elusive. We used a microscopic worm to identify a protein, RTEL1, which possesses many of the properties of Srs2. We then looked at human RTEL1 and found that it acted in the same way, which is extremely exciting."

The scientists went on to find that when the RTEL1 protein was isolated from human cells, it was able to counteract DNA repair events in a test tube, revealing the mechanism through which it is able to prevent inappropriate DNA repair events.

Dr Boulton added: "RTEL1 is fundamentally important in ensuring that DNA damage is repaired correctly, preventing DNA rearrangements. We think this finding will have important implications for understanding cancer as RTEL1 is amplified in certain human tumours."

Dr Lesley Walker, Cancer Research UK's director of cancer information said: "Establishing RTEL1’s role in human cells, allows us to start to think about how we might protect cells from DNA damage that is caused when this protein is amplified. This opens up the possibility for new avenues of drug development in the future which is very encouraging."

ENDS

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Notes to Editor

Louise J Barber et al. RTEL1 maintains genomic stability by suppressing homologous recombination (2008). Cell.

** RTEL1 - is the human equivalent of a protein in yeast called Srs2. Srs2 is a type of enzyme called an anti-recombinase, which is essentially a protein molecule that prevents inappropriate rearrangements of DNA sequences in cells. It therefore acts as a "protector of the genome" because it prevents an inappropriate process of physical rearrangement that can occur in our chromosomes, which could potentially lead to cancer. Amplification of RTEL1 in cells is predicted to interfere promiscuously with normal DNA repair events, which is likely to drive tumour formation.

About the London Research Institute

The Cancer Research UK London Research Institute (LRI) conducts innovative basic biological research to improve our understanding of cancer. The LRI has 550 staff and students and houses 46 research groups based at two locations: Lincoln's Inn Fields laboratories in central London, and Clare Hall laboratories on London's outskirts at South Mimms, Hertfordshire. For more information visit www.london-research-institute.co.uk

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