Summary of article Tuning BRCA1 and BARD1 activity to investigate RING ubiquitin ligase mechanisms. Mikaela D Stewart, Emily D Duncan, Ernesto Coronado, Paul A DaRosa, Jonathan N Pruneda, Peter S Brzovic, Rachel E Klevit. Protein Sci 2017 Mar;26(3):475-483. doi: 10.1002/pro.3091. Epub 2017 Jan 23. PMID: 27977889 PMCID: PMC5326557 DOI: 10.1002/pro.3091 https://pubmed.ncbi.nlm.nih.gov/27977889/

Genes are pieces of the genome that carry the codes required to synthesize each protein in our body. Some genes make us more susceptible to developing certain diseases. One gene, called BRCA1, can lead to high risk for breast and ovarian cancer. It encodes a protein that bears the same name, BRCA1, which is a tumor suppressor.

Although the gene was discovered and sequenced in the early 90s, the function of the BRCA1 protein is still not fully understood. 

Proteins, especially large ones like BRCA1, are often divided into regions based on the specific functions they perform. One region of the protein BRCA1, called the RING domain, is responsible for linking together certain molecules.

This study aimed to identify components of the RING domain that contribute to its function and to uncover their role in the overall activity of BRCA1.

The researchers had previously obtained the 3D structure of the RING domain using NMR (nuclear magnetic resonance), which guided their efforts. They discovered that some components at specific positions in the RING domain can tune the level of the BRCA1 activity up or down, by either inactivating it or by fueling a hyperactivity.

These results are important because they show that it is possible to tune the activity of BRCA1. Given that BRCA1 is a tumor suppressor, the ability to tune the BRCA1 activity in individuals who carry a mutant BRCA1 gene could represent a way to control the development of the disease.