biostudies-literatureDaniloski ZNCI NIH HHSNIHDepartment of Defense5530-5542https://www.ebi.ac.uk/biostudies/studies/S-EPMC5645240biostudies-literatureUnknown77(20)Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The <i>STAG2</i> gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how <i>STAG2</i> loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in <i>STAG2</i> mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in <i>STAG2</i> mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitorCancer researchLoss of Tumor Suppressor <i>STAG2</i> Promotes Telomere Recombination and Extends the Replicative Lifespan of Normal Human Cells.PMC5645240R01CA200751W81XWH-16-1-0590R01 CA200751Smith SDaniloski ZfalseLoss of Tumor Suppressor <i>STAG2</i> Promotes Telomere Recombination and Extends the Replicative Lifespan of Normal Human Cells.Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The <i>STAG2</i> gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how <i>STAG2</i> loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in <i>STAG2</i> mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in <i>STAG2</i> mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitor2017-01-01T00:00:00Z2017 Oct2025-04-03T23:54:18.432Z2019-03-27T00:01:38ZS-EPMC56452402881902910.1158/0008-5472.can-17-126010.1158/0008-5472.CAN-17-1260