Beomseok Seo1,*, Chuna Kim1,*, Mark Hills2,*, Sanghyun Sung1, Hyesook Kim1, Eunkyeong Kim1, Daisy S. Lim1, Hyun-Seok Oh3, Rachael Mi Jung Choi3, Jongsik Chun3, Jaegal Shim4 & Junho Lee1,5
1 Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea. 2 Terry Fox Laboratory, BC Cancer Agency, Vancouver, Canada V5Z 1L3. 3 Department of Biological Sciences, Bioinformatics Institute, BIO-MAX, Seoul National University, Seoul 08826, Korea. 4 Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Korea. 5 Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea.
* These authors contributed equally to this work.
Correspondence to : Junho Lee
Cells surviving crisis are often tumorigenic and their telomeres are commonly maintained through the reactivation of telomerase. However, surviving cells occasionally activate a recombination-based mechanism called alternative lengthening of telomeres (ALT). Here we establish stably maintained survivors in telomerase-deleted Caenorhabditis elegans that escape from sterility by activating ALT. ALT survivors trans-duplicate an internal genomic region, which is already cis-duplicated to chromosome ends, across the telomeres of all chromosomes. These ‘Template for ALT’ (TALT) regions consist of a block of genomic DNA flanked by telomere-like sequences, and are different between two genetic background. We establish a model that an ancestral duplication of a donor TALT region to a proximal telomere region forms a genomic reservoir ready to be incorporated into telomeres on ALT activation.