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ABSTRACT
Because DNA polymerase cannot replicate telomeric DNA at linear chromosomal ends, eukaryotes have developed specific telomere maintenance mechanisms (TMMs). A major TMM involves specialized reverse transcriptase, telomerase. However, there also exist various telomerase-independent TMMs (TI-TMMs), which can arise both in pathological conditions (such as cancers) and during evolution. The TI-TMM in cancer cells is called alternative lengthening of telomeres (ALT), whose mechanism is not fully understood. We generated stably maintained telomerase-independent survivors from C. elegans telomerase mutants and found that, unlike previously described survivors in worms, these survivors “mobilize” specific internal sequence blocks for telomere lengthening, which we named TALTs (templates for ALT). The cis-duplication of internal genomic TALTs produces “reservoirs” of TALTs, whose trans-duplication occurs at all chromosome ends in the ALT survivors. Our discovery that different TALTs are utilized in different wild isolates provides insight into the molecular events leading to telomere evolution.
Abbreviations
| TMM | = | telomere maintenance mechanism |
| ALT | = | alternative lengthening of telomeres |
| TALT | = | templates for ALT |
| TI-TMM | = | telomerase-independent telomere maintenance mechanism |
| EMS | = | ethyl methanesulfonate |
| DDR | = | DNA damage response |
| DSB | = | double strand break |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Dr. Beomseok Seo and Eunkyeong Kim (Seoul National University) for discussion on the manuscript.
Funding
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI14C1277)