In the last four years, the applicant's research group has documented human telomere shortening, telomerase activation in immortalization and cancer, and established a model that is now widely being tested for the role of telomerase in tumor progression. This group further cloned the RNA component of human and mouse telomerase, and characterized the expression in normal cells and in cancer. Goals in the present application will be: i) to characterize the structure and function of the human telomerase RNA component; ii) to clone the protein components of telomerase; and iii) to determine the pathways that regulate telomerase in normal human cells. When all of the cloned components are in hand, and sufficient information has been gained concerning telomerase regulation, it should become possible to devise direct experimental tests of the role of telomerase in aging and cancer. This basic understanding is essential to evaluate the efficacy and potential toxicity of approaches that are being developed to target telomerase in anti-cancer therapies.
| Alder, Jonathan K; Hanumanthu, Vidya Sagar; Strong, Margaret A et al. (2018) Diagnostic utility of telomere length testing in a hospital-based setting. Proc Natl Acad Sci U S A 115:E2358-E2365 |
| Greider, Carol W (2016) Regulating telomere length from the inside out: the replication fork model. Genes Dev 30:1483-91 |
| Lee, Stella Suyong; Bohrson, Craig; Pike, Alexandra Mims et al. (2015) ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells. Cell Rep 13:1623-32 |
| Tom, Hui-I Kao; Greider, Carol W (2010) A sequence-dependent exonuclease activity from Tetrahymena thermophila. BMC Biochem 11:45 |
| Chen, Jiunn-Liang; Greider, Carol W (2005) Functional analysis of the pseudoknot structure in human telomerase RNA. Proc Natl Acad Sci U S A 102:8080-5; discussion 8077-9 |
| Chen, Jiunn-Liang; Greider, Carol W (2003) Determinants in mammalian telomerase RNA that mediate enzyme processivity and cross-species incompatibility. EMBO J 22:304-14 |
| Chen, Jiunn-Liang; Greider, Carol W (2003) Template boundary definition in mammalian telomerase. Genes Dev 17:2747-52 |
| Chen, Jiunn-Liang; Opperman, Kay Keyer; Greider, Carol W (2002) A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA. Nucleic Acids Res 30:592-7 |
| Le, S; Sternglanz, R; Greider, C W (2000) Identification of two RNA-binding proteins associated with human telomerase RNA. Mol Biol Cell 11:999-1010 |
| Le, S; Zhu, J J; Anthony, D C et al. (1998) Telomerase activity in human gliomas. Neurosurgery 42:1120-4;discussion 1124-5 |
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