Reversing Cancer-Causing Faults in the Breast Cancer Gene BRCA2.

Inherited faults (‘mutations’) in the breast cancer gene, BRCA2, can lead to cancers of the breast, ovary or other organs. BRCA2 codes for a protein containing 3,418 building blocks (called ‘amino acids’) in human cells. Surprisingly, certain BRCA2 mutations that cause cancer affect just a single building-block out of over three thousand.

Ashok Venkitaraman’s laboratory has discovered how such a subtle change in BRCA2 might cause cancer, and also how this effect might be reversed. Instead of traveling to the cell nucleus, where they normally repair damage to our DNA and safeguard the information encoded in our genome, these mutations make BRCA2 proteins accumulate in the cytoplasm. Interestingly, these effects can be reversed by another protein, called DSS1, which acts as a chaperone for mutant BRCA2 and helps it to reach the cell nucleus and work correctly again. These findings hold out the future hope of designing drugs that mimic the chaperone protein, to prevent or delay cancer in patients who inherit certain faults in BRCA2.

The team’s findings were published in the journal Nucleic Acids Research on 12 May 2021.

Prof. Venkitaraman said,

“It is very rewarding to have discovered how certain types of mutations affecting the BRCA2 breast cancer gene may cause cancer, and more importantly, to see how we might use this new information to develop drugs that prevent or delay cancer in families who are unfortunate enough to inherit faulty BRCA2. I am very grateful to the Gray Foundation in New York for having supported our research.”