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Dr. Chantal Autexier, Associate Professor
Departments of Anatomy and Cell Biology, and Medicine, McGill University

 

  
Telomeres, the ends of chromosomes, serve as protective caps that prevent chromosomes from fusing together and causing DNA rearrangements that can lead to karyotypic changes and genomic instability. Conventional semi-conservative DNA replication does not allow for the completion of chromosome ends, so telomere length is predicted to decrease with successive rounds of cell division and replication. In ciliates, mammals, vertebrates and yeast, telomere synthesis and replication are generally catalyzed by telomerase, a specialized reverse transcriptase that maintains telomere length by balancing telomere shortening with telomere elongation. Telomerase is a ribonucleoprotein (RNP) in which part of the RNA component provides the template for the synthesis of telomeric sequences. In Tetrahymena and yeast, changes in telomere sequences resulting from altered telomerase RNA templates cause a deregulation of telomere length and eventual cell death. Thus, telomerase is a critical player in telomere maintenance. In most human somatic cells, contrary to cells of the germline, telomeres shorten with age, and telomerase is generally absent. It has been proposed that telomere length may signal exit from the cell cycle, and senescence. Many immortalized and tumour cells have active telomerase leading to the proposal that one of the requirements for immortalization, and possibly carcinogenesis, may be the activation of telomerase. Recently it was demonstrated that the expression of telomerase, in conjunction with alterations in p53, Rb and Ras converts some primary cells into tumorigenic cells. Moreover, inhibiting telomerase results in telomere loss, chromosome damage, and cell death of various human cancer cell lines, validating the search for telomerase inhibitors as anticancer therapies.

Dr. Autexier’s research aims to establish a molecular base for the development of anticancer therapies that target telomerase or telomere integrity and the efficacious treatments of age-related cell death. Studies in the lab are focused on characterizing the mechanisms that regulate the telomerase ribonucleoprotein, telomere length and cell viability, evaluating the principle of anti-cancer treatments that target telomerase or telomere integrity in combination with chemotherapeutics and identifying and characterizing protective functions of telomerase in neuronal and immortal human cells.

SOME RECENT PUBLICATIONS:

Shawi, M. and Autexier, C. 2007. Telomerase, senescence and aging. Mechanisms of Ageing and Development, in press doi: 10.1016/j.mad.2007.11.007

Marie-Egyptienne, D.T., Brault, M.E., Zhu, S. and Autexier, C. 2008. Telomerase inhibition in a mouse cell line with long telomeres leads to rapid telomerase reactivation. Exp. Cell Res. 314, 668-675. MEDLINE link to this publication

Fakhoury, J., Nimmo, G.A.M. and Autexier, C. 2007. Targeting cancer with telomerase immunotherapy. Anti-Cancer Agents in Medicinal Chemistry 7, 475-483.

Brault , M.E. , D’Souza, Y. and Autexier, C. 2007. Telomerase structure, function and evolution. In: Origin and Evolution of Telomeres. Lubo Tomaska and Jozef Nosek, eds. Eureka.com and Kluwer Academic/Plenum Publishers, New York , NY .

Jain, P., Cerone, M.A, LeBlanc, A.C. and Autexier, C. 2007. Telomerase and neuronal marker status of differentiated NT2 and SK-N-SH human neuronal cells and primary human neurons. Journal of Neuroscience Research, 85, 83-89 . MEDLINE link to this publication

Marie-Egyptienne, D.T. and Autexier, C. 2006. Anomalies du complexe de la télomérase en pathologie hématologique. Hématologie, 12, 267-273.

Autexier, C. and Lue, N.F. 2006. The structure and function of Telomerase Reverse Transcriptase (TERT). Annual Review of Biochemistry, 75, 493-517. MEDLINE link to this publication

Cerone M.A., Londono-Vallejo J.A. and Autexier C. 2006. Mutated telomeres sensitize tumor cells to anti-cancer drugs independently of telomere shortening and mechanisms of telomere maintenance. Oncogene 25, 7411-7420. MEDLINE link to this publication

Cerone M.A., Londono-Vallejo J.A. and Autexier C. 2006. Telomerase inhibition enhances the response to anti-cancer drug treatment in human breast cancer cells. Molecular Cancer Therapeutics, Mol. Cancer Ther. 5,1669-1675 . MEDLINE link to this publication

Marie-Egyptienne, D.T., Cerone, M.A. and Autexier, C. 2005. A human-Tetrahymena pseudoknot chimeric telomerase RNA reconstitutes a nonprocessive enzyme in vitro that is defective in telomere elongation. Nucl. Acids Res., 33, 5446-5457. MEDLINE link to this publication

Moriarty, T.J. Marie-Egyptienne, D.T. and Autexier, C. 2005. Regulation of the 5' template usage and incorporation of non-cognate nucleotides by human telomerase. RNA, 11, 1448-1460. MEDLINE link to this publication

Cerone M.A., Autexier, C. Londono-Vallejo J.-A. and Bacchetti, S. 2005. A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT. Oncogene. 24, 7893-7901. MEDLINE link to this publication

Lue N.F., Bosoy D., Moriarty T.J., Autexier C., Altman B., Leng S. 2005. Telomerase can act as a template- and RNA-independent terminal transferase. Proc Natl Acad Sci USA. 102, 9778-9783.

Ward, R.J. and Autexier, C. 2005. Pharmacological Telomerase Inhibition can Sensitize Drug-Resistant and Drug-Sensitive Cells to Chemotherapeutic Treatment. Mol. Pharmacol. 68, 779-786.

Moriarty, T.J., Ward, R.J. Taboski, M.A.S. Autexier, C. 2005. An Anchor Site-type Defect in Human Telomerase that Disrupts Telomere Length Maintenance and Cellular Immortalization. Mol Biol Cell. 16, 3152-3161. MEDLINE link to this publication

Cerone M.A., Ward R.J., Londono-Vallejo J.A., Autexier C. 2005. Telomerase RNA Mutated in Autosomal Dyskeratosis Congenita Reconstitutes a Weakly Active Telomerase Enzyme Defective in Telomere Elongation.
Cell Cycle. 4, 585-589. MEDLINE link to this publication

Cerone, M.A., Ward, R.J. and Autexier, C. 2005. Telomere- and Telomerase-based Therapies. In: Aging Interventions and Therapies. Suresh I.S. Rattan, ed. World Scientific Publishers, Singapore .


Investigators
  

Dr. Chantal Autexier
Dr. Howard Bergman
Dr. Howard Chertkow
Dr. Gustavo Duque
Dr. Andrea LeBlanc

Dr. Hemant Paudel
Dr. Stéphane Richard
Dr. Uri Saragovi
Dr. Hyman Schipper
Dr. Eugenia Wang

 

 

  
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