US researchers say that they have identified a gene that needs to be investigated as a possible breast cancer gene in future studies.
The gene detected by the researchers is Rap80, which is required for the normal DNA-repair function of the well-known breast cancer gene BRCA1.
The efforts of researchers at the Abramson Family Cancer Research Institute of the University of Pennsylvania and the Dana-Farber Cancer Institute, a major affiliate of Harvard Medical School, have led to this identification.
In the study, published in the journal Science, the researchers found Rap80 binds to the region of the BRCA1 protein that is necessary for recognising sites of DNA damage.
They say that cancer-causing mutations in the protein fail to bind to the Rap80 protein, disabling BRCA1 to identify DNA damage sites in the genome. As a result of this, cancer-causing mutations accumulate, spawning the development of breast and ovarian malignancies.
"With this current discovery, we have made significant new insights into the molecular mechanism by which BRCA1 recognises sites of DNA damage that breast-cancer-causing mutated forms of BRCA1 cannot recognise," says co-senior author Dr. Roger Greenberg, Assistant Professor of Cancer Biology at Penn.
"Now we have gained a partial understanding of the molecular basis between cancer-causing BRCA1 failures to fix DNA damage versus normal BRCA1's ability to fix DNA damage," he adds.
The researchers say that Rap80 enables BRCA1 to be recruited to sites of damage by binding to specific types of the ubiquitin protein, which is tightly bound to DNA.
Since BRCA1 and BRCA2 mutations account for less than 50 per cent of inherited breast cancer, boffins are of the opinion that the Rap80 gene is a candidate to investigate as another breast cancer disease gene in families that though have a history of the disease, do not have such mutations.
"Thus Rap80, by interacting with a BRCA1 region that is essential for BRCA tumour suppression, now becomes a candidate to investigate as another breast cancer disease gene in families that do not have BRCA1 and BRCA2 mutations, but have a history of breast and/or ovarian cancer," says Greenberg.
"In collaboration with other researchers we are currently looking to see if families that have a history of breast cancer, but lack BRCA1 and BRCA2 mutations, have any gene sequence changes in Rap80," he adds.