Scientists uncover structure, mechanisms of BRCA2 protein

For the first time, researchers from the United Kingdom have created pictures of the BRCA2 protein. Mutations in the gene that encodes this protein are well known to increase the risk of breast and ovarian cancers. 

Uncovering the structure and mechanisms of the protein may pave the way for treatments targeting BRCA2 gene mutations, according to the investigators.

Researchers have created pictures of the structure and mechanisms of the BRCA2 protein for the first time, which may pave the way for treatments targeting BRCA2 gene mutations.
Image credit: Imperial College London, Cancer Research UK

The research team at the Department of Medicine at Imperial College London, publish their findings in the journal Nature Structural and Molecular Biology.

Around 45% of women who have a BRCA2 gene mutation will develop breast cancer by the time they are 70 years old, compared with 12% of women in the general population. 

While 1.4% of women in the general population will develop ovarian cancer at some point in their lives, this will happen for 11-17% of women with a BRCA2 gene mutation.

However, it has been challenging to develop treatments that target BRCA2 gene mutations.

Researchers know the BRCA2 protein plays a part in DNA repair. Any mutations in the gene that encodes the protein can hinder this repair process and cause cancer. However, the mechanisms behind the DNA repair activity of BRCA2 and the structure of the protein have remained a mystery, until now.

Findings 'improve understanding of a fundamental cause of cancer'

The researchers were surprised to find that the BRCA2 proteins work in pairs, and each pair works with another protein called RAD51.

RAD51 molecules convene on strands of broken DNA with the help of the BRCA2 proteins. The RAD51 molecules then form filaments that look for matching DNA strands that will repair the broken DNA.

Furthermore, the researchers discovered that each pair of BRCA2 proteins attach to two sets of RAD51 molecules that point in opposing directions. They explain that this is so the RAD51 molecules can repair broken DNA strands that face either direction.

In addition, the team found that the BRCA2 proteins assist the RAD51 molecules in forming short filaments on numerous DNA regions. They say this may be to boost efficiency in finding matching DNA strands.

From their findings, the research team has created a set of pictures detailing the shape, structure and mechanisms of the BRCA2 protein.

Commenting on their discovery,the discovery team says:

"This study improves our understanding of a fundamental cause of cancer. It's our first view of how the protein looks and how it works, and it gives us a platform to design new experiments to probe its mechanism in greater detail.

Once we have added more detail to the picture, we can design ways to correct defects in BRCA2 and help cells repair DNA more effectively to prevent cancer. We can also think about how to make the repair process less effective in cancer cells, so that they die."

October is Breast Cancer Awareness Month. In line with this campaign, a recent spotlight feature from this Blog www.emersonblognews.blogspot.com investigated whether men are the forgotten victims of breast cancer.