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Prach Siriviriyakul

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Chromosome must be protected

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

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However, telomeres also play other important roles in cell

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Lets review DNA replication

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End of replication problem

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Telomerase

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How telomerase work

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

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

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Protective function Chan and Blackburn, 2003

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Telomerase in cancer cell cancer cell

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Telomerase in cancer cell

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This event certainly require telomerase

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

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

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

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Telomerase and Aging Cawthon et al, 2003

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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

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Chronic stress and telomere Blackburn et al, 2004

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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.

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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