STAG1 is a component of cohesin, a ring-shaped protein complex involved in sister chromatid cohesion (SCC) that also plays important roles in the maintenance of chromatin structure, gene expression, and DNA repair. Cohesin consists of a core trimer and one of two mutually exclusive variant STAG subunits, STAG1 and STAG2. STAG1 is thought to primarily regulate telomeric cohesion, whereas STAG2 is primarily involved in centromeric cohesion (1,2). STAG2 mutations were detected in bladder cancer, Ewing sarcoma and acute myeloid leukemia. Targeting STAG1 represents a therapeutic opportunity in the treatment of STAG2-mutant cancers. Studies demonstrate that partial suppression of STAG1 triggers strong and selective anti-proliferative effects in STAG2-mutant cancer models (3).
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1. Hill VK, Kim JS, Waldman T. Cohesin mutations in human cancer. Biochim Biophys Acta. 2016;1866(1):1-11.
2. Arruda NL, Carico ZM, Justice M, Liu YF, Zhou J, Stefan HC, Dowen JM. Distinct and overlapping roles of STAG1 and STAG2 in cohesin localization and gene expression in embryonic stem cells. Epigenetics Chromatin. 2020 Aug 10;13(1):32.
3. van der Lelij P, Newman JA, Lieb S, et al. STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancers. Life Sci Alliance. 2020;3(7): e202000725.
4. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
5. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.
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