Identification of mechanism of cancer-cell-specific reactivation of hTERT offers therapeutic opportunities for blocking telomerase specifically in human colorectal cancer

Semih Can Akıncılar, Joelle Yi Heng Chua, Qin Feng Ng, Claire Hian Tzer Chan, Zahra Eslami-S, Kaijing Chen, Joo-Leng Low, Surendar Arumugam, Luay Aswad, Clarinda Chua, Iain Beehuat Tan, Ramanuj DasGupta, Melissa Jane Fullwood, Vinay Tergaonkar

Nucleic Acids Research, gkac479, https://doi.org/10.1093/nar/gkac479

Healthy and cancer cells harbor the same DNA sequence, but reactivation of the Human Telomerase Reverse Transcriptase (hTERT) gene is observed only in cancer cells. How does that happen was not known for over three decades of research? This study identifies a specific DNA structure that forms only in cancer cells and brings the necessary molecular machinery into the correct position to activate the hTERT gene. The detailed mechanism of hTERT activation provided in this study will be instrumental in designing cancer cell-specific hTERT inhibitors, especially since all the other ways of inhibiting telomerase failed in the clinic.

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