The protein of breast cancer, BRCA2, was finally purified

The protein associated with breast cancer, BRCA2, has finally been purified through the work done by three different teams. The results of 15 years of research relaunch the fight against the most common cancer among women.

Fifteen years ago the scientific community stalking and three independent laboratories are reaching the end simultaneously: the BRCA2 protein (Breast cancer type 2 susceptibility protein), which many mutations lead to breast cancer, is now purified. This protein is known since 1995 and its role is more or less well defined: it is a tumor suppressor, to repair DNA damage in the event.

The purification of a protein allows to study it from every angle. She can put the protein into contact with other protein partners or to determine the precise nucleic its biological role. The protein can also be crystallized to determine the structure and thus open up avenues for discovering molecules that can interact with it or inhibit its function.

But the purification of a protein is fraught with pitfalls. Each step can quickly become a problem: cloning the gene, the protein expression in cells (specially modified to secrete large quantities of the inserted gene product), the separation of protein from all other components of the cell , its solubilization ...

The success of the purification of BRCA2 was not a foregone conclusion, especially as its large size (3418 amino acids) is not an asset. It would even the first ever purified protein as long. However, it has now been done, although it took at one of the researchers four years to the only optimization of purification.

While the structure of the BRCA2 protein is pending, that of its partner protein RAD51 (the yeast Saccharomyces cerevisiae), is already known. Protein Data Base ©

Role confirmed or BRCA2 in the repair of DNA

One of three teams (University of California, Davis) has extracted the protein from human kidney epithelial cells. Researchers at UC Davis Cancer Center have, meanwhile, purified protein from yeast cells. The third team, based at Cancer Research UK in London, preferred use of epithelial cells cancerous. The three teams that have each published their results in Nature and Nature Structural & Molecular Biology, added "tags", that is to say, peptides fused end to improve protein solubility and folding of BRCA2 and thereby promoting stability.

Subsequent studies performed on the purified protein have confirmed some of its features already assumed, unsurprisingly. Thus, BRCA2 promote the action of the RAD51 recombinase named. It would increase the specificity of interaction of RAD51 with single-stranded DNA and stimulate its ability to exchange a fragment of DNA-damaged DNA correctly. Researchers have also shown that there is monomeric and dimeric forms of the BRCA2 protein, according to observations by electron microscopy.

Subsequent experiments should provide further responses, including changing the sequence of the protein profile of mutations observed in patients and then observing the effect on the properties of BRCA2 (this time by purifying the mutant protein). Furthermore, the crystallization of the protein to obtain its structure is in progress, but again the optimization can be time consuming.

Breast cancer is stimulated by mutations in the BRCA2 protein. The purification of this protein, expected for 15 years, will certainly accelerate the fight against this scourge. Credits DR