Cohesin subunit SA-1 (STAG1) (STAG1)

Cohesin subunit SA-1 (STAG1) is a core component of the cohesin complex, a ring-shaped multi-protein assembly that mediates sister chromatid cohesion, DNA repair, and the regulation of gene expression through chromatin looping (UniProt: Q8WVM7). In human cells, the cohesin complex requires one of two paralogous subunits, STAG1 or STAG2, to function effectively. While these subunits are often redundant in healthy tissues, STAG2 is frequently inactivated by mutations in various malignancies, including bladder cancer, Ewing sarcoma, and acute myeloid leukemia (van der Lelij et al., 2017, Nature Communications). This creates a state of synthetic lethality where the survival of STAG2-mutated cancer cells becomes entirely dependent on the remaining STAG1 subunit. Therapeutic strategies targeting SA1 mRNA, such as antisense oligonucleotides (ASOs) or siRNA, aim to selectively eliminate these cancer cells by inducing catastrophic chromosome segregation errors and apoptosis while sparing healthy cells that express functional STAG2 (Benedetti et al., 2017, Nature Communications). As such, STAG1 represents a high-priority precision medicine target for tumors harboring cohesin mutations (Hill et al., 2016, Molecular Cancer Research).

Other names

SA1Stromal antigen 1SCC3 homolog 1STAG1Cohesin subunit SA-1

Synthetic lethality in STAG2-deficient cells via disruption of the cohesin complex (van der Lelij et al., 2017, Nature Communications)