Genome-wide screens identify specific drivers of mutant hTERT promoters

• DOI: 10.1073/pnas.2105171119
• Publication Date: 2022-01-13T21:40:35Z
• Authors: Raghuvaran Shanmugam; Mert Burak Ozturk; Joo-Leng Low; Semih Can Akincilar; Joelle Yi Heng Chua; Matan Thangavelu ...; Giridharan Periya...; Ramanuj DasGupta; Vinay Tergaonkar
• Keywords: Gene Editing; 0301 basic medicine; Mediator Complex; Transcription, Genetic; Biological Sciences; Regulatory Sequences, Nucleic Acid; Chromatin; 3. Good health; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Line, Tumor; Neoplasms; Mutation; Humans; CRISPR-Cas Systems; Promoter Regions, Genetic; Telomerase; Transcription Factors

Significance

Mutations in hTERT promoter are seen in over 19% of human cancers, irrespective of the cancer type. Understanding the molecular players that regulate Mut- hTERT promoters may help the design of effective targeting strategies to inhibit telomerase reactivation specifically in cancer cells. Our work uses genome-wide functional screens to identify 30 specific regulators of Mut- hTERT promoters. These candidates identified from the screening serve as an excellent resource to understand how telomerase is reactivated and as targets for making inhibitors to telomerase, a key driver of cancer.