A new study demonstrates the mechanism of how amplification of EMSY contributes to cancer. The paper "The EMSY threonine 207 phospho-site is required for EMSYdriven suppression of DNA damage repair" appears in the journal Oncotarget. Researchers of the study include Petar Jelinic, Monicka Wielgos and Douglas A. Levine from NYU Langone Medical Center, and Laura Eccles, Jill Tseng, Paulina Cybulska and Simon Powell from Memorial Sloan Kettering Cancer Center. Yearly, 8.8 million people die from cancer. Breast cancer is the most prevalent cancer among women across all races. Although breast cancer primarily affects women, men can also develop the disease. Breast cancer is not a single disease. Many genetic alterations contribute to it. The diversity of breast cancer tumors makes treatment complex. Ovarian cancer is is the seventh most common cancer in women worldwide. In the USA, the disease is diagnosed in an estimated 20,000 women every year. In the UK, about 7,000 new cases of ovarian cancer were diagnosed yearly. Ovarian cancer often starts silently, not showing symptoms until its later stages, which decreases the survival rate. BRCA1 and BRCA2, which are tumor suppressor genes, are essential for the repair of double-strand DNA breaks. Mutations in BRCA have been identified as a hallmark of breast and ovarian cancer. So a blood test is being used to determine whether a woman carries an inherited BRCA mutation. The test helps predict which women are more likely to develop breast and ovarian cancer. However, some women with normal BRCA also develop these cancers. In this study, the research team looked at another gene called EMSY. This gene is amplified in about 11% of high-grade ovarian cancer patients. Previously, scientists thought that amplification of EMSY disrupts DNA damage repair by suppressing BRCA2 function. But this study demonstrated that EMSY actually acts independently of BRCA. Lead researcher Douglas A. Levine and colleagues studied the full-length EMSY protein. They found that EMSY overexpression impairs the DNA damage repair process. Moreover, an amino acid in the EMSY protein plays a key role in EMSY-driven suppression of DNA damage repair. When the activity of EMSY is increased, an enzyme called PKA directly reacts with this amino acid, which inhibits the repair of DNA damage. Collectively, like mutations in BRCA, alterations in EMSY also impair DNA repair process and increase the risk of cancer. According to study first author Petar Jelinic, drugs for BRCA-driven cancer may have therapeutic effect on EMSY-driven cancer. The study helps us understand why some women with healthy BRCA1 and BRCA2 genes still develop cancer and may expand the population of patients who could benefit from targeted therapies. In addition, Cusabio provides proteins and antibodies including BRCA, EMSY, PKA, and Recombinant NPY1R for researchers doing related experiments.
