A Common Cancer Risk-Associated Allele in the hTERT Locus Encodes a Dominant Negative Inhibitor of Telomerase
Fig 3
INS1b overexpression results in shorter telomeres and increased telomeric DNA damage response.
(A) Terminal restriction fragment (TRF) length analysis of stably-transfected HT1080 cells at increasing population doublings (PD). (B) Metaphase telomere dysfunction-induced foci (Meta-TIF) analysis of stably-transfected HT1080 cells at PD33 (top) and PD190 (bottom). Metaphase cells were stained using γ-H2AX immunofluorescence (red), telomere FISH (green) and DAPI (blue). Meta-TIFs are indicated by yellow arrow heads. (C) Quantification of meta-TIFs calculated by the percentage of chromosome ends stained with γ-H2AX at one or both chromatids in each metaphase spread (mean ± SEM; P-value calculated by two-tailed Student’s t test; ** p≤0.01, compared to Empty Vector control at PD33 or PD190).