The variant of the BRCA1 gene, which underlies increased risk of ovarian and breast cancer, has lost its ability to change shape and repair DNA, researchers have reported.
When healthy, the gene is known to make a protein which helps repair damage to broken DNA, but in people with a mutated BRCA1 gene, DNA damage accumulates over time.
A team from the University of Birmingham, UK, examined the action of the gene more closely and found that it changes shape to protect vulnerable DNA when the copying machinery is broken – until the repair is complete.
This protective role of BRCA1 in DNA-copying is disabled in people with faulty BRCA1, while the copying machinery is being repaired.
The new research is published in Nature today yesterday.
Dr Manolo Daza-Martin said: "Previous research has shown us that in cells the BRCA1 gene makes a protein that helps repair damage to broken DNA. Therefore, people who inherit a faulty BRCA1 gene are less able to repair damage that inevitably accumulates in their DNA over time – putting them at higher risk of ovarian and breast cancer.
“It was surprising to find out that BRCA1 changes shape depending on the type of damage it finds at the scene, and this shape change alters the way the cell responds."
Co-author Professor Jo Morris added: "Our research could be important for understanding how cancers develop and means we could have identified a new way of suppressing tumours.
"We are a long way from it, but ultimately this may alter how cancer patients are treated. We will now continue this important research into the role of BRCA1’s DNA copying function in cancer development."
Daza-Martin, M. et al. Isomerization of BRCA1-BARD1 promotes replication fork protection. Nature 3 July 2019; doi: 10.1038/s41586-019-1363-4
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