A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells.

ABSTRACT: Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% of all cancers. Despite this high prevalence of ALT in cancer, the mechanism and genetics by which cells activate this pathway remain incompletely understood. A major challenge in dissecting the events that initiate ALT is the extremely low frequency of ALT induction in human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human pluripotent stem cells to deterministically induce ALT upon differentiation. Using this genetically defined system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is sufficient

SUBMITTER: Turkalo TK 

PROVIDER: S-EPMC9941109 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature