Loss of Tumor Suppressor STAG2 Promotes Telomere Recombination and Extends the Replicative Lifespan of Normal Human Cells.

ABSTRACT: 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 STAG2 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 STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in STAG2 mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitor

SUBMITTER: Daniloski Z 

PROVIDER: S-EPMC5645240 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature