Journal
NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 21, Issue 7, Pages 384-397Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41580-020-0234-z
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Funding
- NIH [CA197563, AG056575]
- MSTP Training Grant [GM007365]
- Gerald J. Lieberman Fellowship
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Telomerase is a ribonucleoprotein complex, the catalytic core of which includes the telomerase reverse transcriptase (TERT) and the non-coding human telomerase RNA (hTR), which serves as a template for the addition of telomeric repeats to chromosome ends. Telomerase expression is restricted in humans to certain cell types, and telomerase levels are tightly controlled in normal conditions. Increased levels of telomerase are found in the vast majority of human cancers, and we have recently begun to understand the mechanisms by which cancer cells increase telomerase activity. Conversely, germline mutations in telomerase-relevant genes that decrease telomerase function cause a range of genetic disorders, including dyskeratosis congenita, idiopathic pulmonary fibrosis and bone marrow failure. In this Review, we discuss the transcriptional regulation of human TERT, hTR processing, assembly of the telomerase complex, the cellular localization of telomerase and its recruitment to telomeres, and the regulation of telomerase activity. We also discuss the disease relevance of each of these steps of telomerase biogenesis. Telomere length is maintained by telomerase, which comprises a reverse transcriptase and a template RNA. Telomerase activity is disrupted in several genetic disorders, but is commonly increased in cancer. Recent studies have uncovered many regulatory mechanisms of telomerase and how telomerase upregulation in cancer is achieved.
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