Researchers identify enzyme regulating BRCA2 pathway

Volume 6, Issue 1, 2017


The UCHL3 enzyme could help guide precision therapy in BRCA2 cancers.

Photograph of Zhenkun Lou, Ph.D.

Zhenkun Lou, Ph.D.

Researchers at Mayo Clinic have identified a gene called UCHL3 that regulates the BRCA2 pathway, which is important for DNA repair.

Results of this research were published online Dec. 9, 2016, in the journal Genes & Development.

"DNA encodes the blueprints for our body, and DNA repair is a fundamental mechanism to prevent the accumulation of mutations in DNA and human disease," said Zhenkun Lou, Ph.D., a molecular pharmacologist at Mayo Clinic's campus in Rochester, Minnesota, and senior author of the journal article. "The BRCA2 pathway is important for DNA repair, and mutation of the BRCA2 gene is linked to increased cancer risk, especially breast cancer and ovarian cancer."

According to Dr. Lou, UCHL3 is highly expressed in some cancers and mutated or deleted in other cancers. Cancer cells with high UCHL3 expression are resistant to chemotherapy, whereas cancer cells with low UCHL3 are more sensitive to chemotherapy. Therefore, the expression of UCHL3 could be a guide to develop more precise cancer therapy.

"UCHL3 could be a potential therapeutic target to overcome resistance to chemotherapy in cancer cells that have a high level of UCHL3," Dr. Lou said.

The UCHL3 gene could also be developed into a biomarker in the clinic to guide precision medicine.

"While more research is needed, our studies may provide a novel therapeutic venue to treat women's cancers and thereby contribute to the health and welfare of women," Dr. Lou said.