Acute telomere deprotection prevents ongoing BFB cycles and rampant instability in p16^INK4a-deficient epithelial cells.

ABSTRACT: Telomere dysfunction drives chromosome instability through endless breakage-fusion-bridge (BFB) cycles that promote the formation of highly rearranged genomes. However, reactivation of telomerase or ALT-pathway is required for genome stabilisation and full malignant transformation. To allow the unrestricted proliferation of cells at risk of transformation, we have established a conditional system of telomere deprotection in p16^INK4a-deficient MCF-10A cells with modified checkpoints. After sustained expression of a dominant negative form of the shelterin protein TRF2 (TRF2^ΔBΔM), cells with telomere fusion did progress to anaphase but no signs of ongoing BFB cycles were observed, thus anticipating proliferation defects. Indeed, 96 h TRF2^ΔBΔM expression result

SUBMITTER: Bernal A 

PROVIDER: S-EPMC6007466 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature