Scientists uncover protective role of BRCA2's 'protein partner'

Cancer Research UK

Cancer Research UK scientists have shed new light on the vital role that a protein plays in protecting our DNA, reveals a study published in Nature Structural and Molecular Biology today (Sunday).

The protein, called Rad51, is already known for its vital role in repairing DNA damage – working with a second protein, BRCA2. Faults in the BRCA2 gene significantly increase the risk of developing breast cancer.

Scientists knew Rad51 was also important for protecting ‘exposed’ DNA when it is being copied for cells to divide. But until now they didn’t understand precisely what this role was and how Rad51 works in this second role.

This was partly because cells can’t usually survive without a working Rad51 protein, which makes them difficult to study in the lab.

To get around this the researchers developed a new technique involving state-of-the-art electron microscope technology to find out what problems occur during DNA replication in the absence of Rad51.

They discovered that without the protection of Rad51, other proteins in the body can attack the DNA. This would cause large-scale damage to the DNA which over time could lead to cancer.

The more we know about the fundamental processes by which DNA copies and repairs itself, the better we can understand what goes wrong, in some cases leading to cancer.

Study leader Dr Vincenzo Costanzo, head of genome stability at Cancer Research UK’s London Research Institute Clare Hall Laboratories, said: “Cells lacking key DNA repair proteins don’t normally survive outside the body, which makes them difficult to study in the lab.

"To overcome this challenge we came up with a completely new technique, which involved removing the Rad51 from a concoction made of frog spawn to see what problems occurred in the DNA.

"This exciting development allowed us to generate some of the first images showing the DNA damage that occurs when Rad51 isn’t there to protect the DNA.

"Before now, such images had only been possible in yeast, which are much further from humans than frogs on the evolutionary scale, so this is an important step forward in understanding how BRCA2 faults lead to cancer."

Dr Helen George, Cancer Research UK’s head of cancer information, said: "This work shows how important the protective role of the Rad51 protein is in the DNA copying process, as well as in DNA repair. Some new cancer drugs exploit the Rad51 repair process. So as well as improving our understanding of cancer, this work could also inform new approaches to treatment."

ENDS

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References

Hashimoto, Y et al, Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis (2010), Nature Structural and Molecular Biology, DOI: 10.1038/nsmb.1927

Notes to Editor

BRCA1 and BRCA2

  • Around 1 in 800 women in the UK carry a faulty BRCA1 gene and 1 in 500 carry a faulty BRCA2 gene.
  • Women carrying the BRCA1 and BRCA2 mutation have a 45-65 per cent chance of developing breast cancer, and a 20-45 per cent chance of developing ovarian cancer, by the age of 70.
  • Risks in carriers of genetic faults vary substantially and understanding these differences can potentially lead to better understanding of an individual’s risk, with implications for the clinical management of these individuals.
  • Genetic testing for faulty BRCA1 and BRCA2 genes is available on the NHS for women with a very strong family history.

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