Telomerase: Cancer and the Philosopher’s Stone
description
Transcript of Telomerase: Cancer and the Philosopher’s Stone
![Page 1: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/1.jpg)
Telomerase: Cancer and the Philosopher’s Stone
Sapana Vora
1 March 2007
Biology 445
![Page 2: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/2.jpg)
Table of Contents
Chapter 1: TelomeresChapter 2: Telomerase: FunctionChapter 3: Telomerase: StructureChapter 4: Telomerase and CancerEpilogueBibliography
![Page 3: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/3.jpg)
Ch.1- Telomeres: Getting the Short End
Specialized nucleoprotein structures at chromosome ends
Repetitive arrays of guanine-rich hexameric DNA and telomere-binding proteins
Protect chromosomes from damage and degradation
telomeretelomere
Human telomeric repeat sequence: 5’- TTAGGG -3’
Page 1
![Page 4: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/4.jpg)
DNA Replication Anyone?
RNA primer for Okazaki fragment
DNA PolymeraseLeading strand
Lagging strandSite of next
primer
5’
3’
5’
3’3’
5’
Page 2
![Page 5: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/5.jpg)
Telomeres during DNA Replication
Lagging strand Okazaki fragments leave unfinished 5’ ends
No complementary strand DNA degrades
Image: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Telomeres.html Page 3
![Page 6: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/6.jpg)
Chromosomal Alzheimer’s in Action
Round 305’3’
3’5’
Round 605’3’
3’5’
Round 905’3’
3’5’
Round 15’3’
3’5’
Page 4
![Page 7: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/7.jpg)
How Do Cells Keep from Dying?
If all cells lost telomeric DNA and thus suffered irreparable DNA damage, immortal cell lines could not exist.
But they do exist: germline cells (including ES cells), adult stem cells, cancer cells
Page 5
![Page 8: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/8.jpg)
Ch.2- Tying Up Loose Ends
Telomerase:Telomerase is a reverse transcriptase that
specifically synthesizes telomeric DNA Is a type of DNA polymerase Promotes stability of chromosomesProtects linear DNA from degradation at
chromosome ends Is repressed in most cell types
Page 6
![Page 9: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/9.jpg)
Ch.3: Of Subunits and Structure
Ribonucleoprotein (made of RNA and protein):
RNA- snoRNA-like (small nucleolar RNA) molecule called TERC (telomere RNA component)
Protein- TERT (telomere reverse transcriptase) provides catalytic action
Page 7
![Page 10: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/10.jpg)
Structure and Action
Page 8
![Page 11: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/11.jpg)
Ch.4- Telomerase’s Role in Cancer
Page 9
![Page 12: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/12.jpg)
Shay, J. W. et al. Hum. Mol. Genet. 2001 10:677-685; doi:10.1093/hmg/10.7.677
Immunohistochemical localization of hTERT protein in normal and cancer cells
Telomerase Activity in Cancer
Page 10
![Page 13: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/13.jpg)
Telomerase: The Philosopher’s Stone
M1 = replicative senescence (arrested proliferation with continued metabolism
M2/crisis = very short telomeres and widespread apoptosis
Page 11
![Page 14: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/14.jpg)
We’ve Seen This Before…
Round 305’3’
3’5’
Round 605’3’
3’5’
Round 905’3’
3’5’
Round 15’3’
3’5’
Page 12
![Page 15: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/15.jpg)
Cancer Cells Do It Differently
Round 15’3’
3’5’
Round 305’3’
3’5’
Round 605’3’
3’5’
Round 905’3’
3’5’
Page 13
![Page 16: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/16.jpg)
Epilogue: Cancer Therapeutics?
Telomerase is expressed almost exclusively in malignant cells…
But…Telomere length varies in different
cancer cellsALT (alternate lengthening of telomeres)
mechanisms
Page 14
![Page 17: Telomerase: Cancer and the Philosopher’s Stone](https://reader035.fdocuments.in/reader035/viewer/2022070403/568139c4550346895da16d1f/html5/thumbnails/17.jpg)
Bibliography
1. Chen, et al. “Secondary Structure of Vertebrate Telomerase RNA.” Cell, 2000. Vol. 100 (5): 503-514
2. Counter, et al. “Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase.” Oncogene, 1998. 16: 1217-1222
3. Granger, et al. “Telomerase in cancer and aging.” Critical Reviews in Oncology/Hematology, 2002. 41 (1): 29-49
4. Hahn. “Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer.” Journal of Clinical Oncology, 2003. Vol. 21 (10): 2034-2043.
5. Kimball’s Biology Pages. John W. Kimball. 23 September 2006. <http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Telomeres.html>
6. Marchetti, et al. “Telomerase Activity as a Prognostic Indicator in State I Non-Small Cell Lung Cancer.” Clinical Cancer Research, 1999. 5: 2077-2081
7. Seimiya, et al. “Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics.” Cancer Cell, 2005. 7:25-37.
8. Shay, et al. “Telomerase and cancer.” Human Molecular Genetics, 2001. Vol. 10 (7): 677-685
9. Stewart, et al. “Telomerase contributes to tumorigenesis by a telomere length-independent mechansim.” PNAS, 2002. Vol. 99 (20): 12606-12611