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Updated: Aug 20, 2026

Analyzing Telomeric Protein-DNA Interactions Using Single-Molecule Magnetic Tweezers
Published on: August 30, 2024
Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics
Hiroyuki Seimiya1, Yukiko Muramatsu, Tomokazu Ohishi
1Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. hseimiya@jfcr.or.jp
Abstract:
Telomere elongation by telomerase is repressed in cis by the telomeric protein TRF1. Tankyrase 1 poly(ADP-ribosyl)ates TRF1 and releases it from telomeres, allowing access of telomerase to telomeres. Here we demonstrate that tankyrase 1 inhibition in human cancer cells enhances telomere shortening by a telomerase inhibitor and hastens cell death. Conversely, either tankyrase 1 upregulation or telomere shortening, each of which decreased TRF1 loading on a chromosome end, attenuated the impact of telomerase inhibition. These results are consistent with the idea that telomeres having fewer TRF1s increase the efficiency of their elongation by telomerase. This study implies that both enzyme activity and accessibility to telomeres can be targets for telomerase inhibition.
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