1. Prach Siriviriyakul

2. Chromosome must be protected

3. Telomere http://publications.nigms.nih.gov/thenewgenetics/chapter2.html TetrahymenaTTGGGG VertebratesTTAGGG S.cerevisiae(TG) 1-6 TG 2-3 Non-coding repeated sequence

4. However, telomeres also play other important roles in cell

5. Let’s review DNA replication

6. End of replication problem

7. Telomerase

8. How telomerase work

9. Telomerase in humans Telomerase presents with high level in various proliferative cells Stem cells Activated lymphocytes Hair follicles Cancer cells Etc.

10. Telomerase in humans Telomerase presents with detectable level in some adult cells Epithelial Fibroblast Endothelial Etc.

11. Protective function Chan and Blackburn, 2003

12. Telomerase in cancer cell cancer cell

13. Telomerase in cancer cell

16. This event certainly require telomerase

18. Telomerase in cancer cell Li et al. 2004; Bagheri et al 2006

19. the high levels of telomerase promote an undifferentiated, “stem-cell-like” phonotype Other experiments support that

20. Knock-down of telomerase inhibits metastasis in vivo mouse melanoma model Kashani-Sabet et al, 2004

21. Telomerase and Aging Cawthon et al, 2003

22. Telomerase and Aging Cawthon et al, 2003 Shorter telomeres 3.2 fold higher mortality rate from heart disease 8.5 fold higher mortality rate from infectious disease

23. Chronic stress and telomere Blackburn et al, 2004

24. As lots of researches suggested that telomere plays important role in cancer and aging, telomere is expected to be the effective target for drug involving aging and cancer.

25. Reference Gerald carp, Cell Biology,6th edition, Wiley. Elizabeth Blackburn, Lecture on telomerase part1-3. www.youtube.com http://www.pharmacy.ubc.ca/faculty_staff/facultysites/jwonglab http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1544082/ Li et al. Genes and pathways downstream of telomerase in melanoma metastasis, 2004. Chan, S. W.-L and Blackburn, E.H. Telomerase and ATM/Tel1p protect telomeres from nonhomologous end joining., 2003