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Telomeres are repeating sequences that allow cells to distinguish the ends of chromosomes from broken DNA ends. Telomerase is an RNA+protein enzyme that solves the end replication problem by elongating telomeres Normal somatic human cells do not express telomerase, so they have a limited lifespan The Hayflick Limit = the number of times a cell can divide before telomeres are critically short Telomerase is essential in human stem Cells in culture and in its absence cells senesce and eventually die One would think that a telomerase knockout mouse would not be able to survive… …but this is not the case! Telomerase knockout mice survive for at least six generations and can develop tumors Telomerase is re-expressed in 90% of human tumors Telomerase re-expression immortalizes cells and contributes to cancer Because it is present in so many tumors, telomerase is an attractive drug target Targeting Telomerase could be an issue since it is necessary for stem cells Works Cited Blasco, Maria A, Han-Woong Lee, M. Prakash Hande, Enrique Samper, Peter M. Lansdorp, Ronald A. DePinho, and Carol W Greider. “Telomere Shortening and Tumor Formation by Mouse Knockout Lacking Telomerase RNA.” Cell. Vol 91 No 1. 3 October 1997 25-34 <http://www.sciencedirect.com.libproxy.lib.unc.edu/science/article/pii/S0092867401800064> De Lange, Titia. “Shelterin: the protein complex that shapes and safeguards human telomeres.” Genes and Development. 2005 vol 19 2100-2110 Greider, Carol W. “Telomerase Discovery: The Excitement of Putting Together Pieces of the Puzzle (Nobel Lecture). Angewandte Chemie International Edition. Vol 49 issue 41 p.7422-7439 4 October 2010. Hamilton, Jon. “Matching DNA with Medical Records to prevent Disease and Aging.” NPR. 19 November 2012. <http://www.npr.org/blogs/health/2012/11/19/165498842/matching-dna-with-medicalrecords-to-crack-disease-and-aging> Hiyama, E and K. Hiyama. “Telomere and Telomerase in Stem Cells.” British Journal of Cancer. Vol 96 No. 7. 2007 1020-1024 <http://www.readcube.com/articles/10.1038/sj.bjc.6603671> Mathon, Nicole F. and Alison C. Lloyd “Box 1: Telomeres and telomerase” from “Milestones in Cell Division: Cell Senescence and Cancer.” Nature Reviews.<http://www.nature.com/nrc/journal/v1/n3/box/nrc1201-203a_BX1.html> Mocellin, Simone, Karen A. Pooley, and Donato Nitti. “Telomerase and the search for the end of cancer.” Trends in Molecular Medicine. February 2013 Vol 19 No 2 Shay, Jerry W., Ying Zou, Eiso Hiyama, and Woodring E. Wright. “Telomerase and Cancer” Human Molecular Genetics. 2001 Vol 10 Issue 7. p 677-685 “Telomere Functioning.” Pharminox. <http://www.pharminox.com/telomere_signalling.aspx>