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The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo
1Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, 620 University Avenue, ON M5G 2C1, Toronto, Canada.
Current Biology : CB
|December 5, 2000
Summary
Mammalian telomerase reverse transcriptase (TERT) is sufficient for telomere maintenance and genomic stability. Disruption of the mTert gene in mice leads to telomere loss and instability, confirming TERT
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Mammalian telomerase, composed of TERT and mTR, maintains telomere length.
- The sufficiency of TERT alone for telomere maintenance and genomic stability is unknown.
- Previous studies highlight the essential roles of both TERT and mTR.
Purpose of the Study:
- To determine if the catalytic core component, mammalian TERT, is sufficient for telomere maintenance.
- To investigate the role of TERT in chromosome stability and cellular processes.
- To compare the phenotypes of mTert-deficient cells with mTR-deficient cells.
Main Methods:
- Gene disruption of the mTert gene in mice.
- Analysis of telomere length in mTert-deficient embryonic stem (ES) cells.
- Assessment of genomic stability, aneuploidy, and telomeric fusions in mTert-deficient ES cells.
Main Results:
- Disruption of the mTert gene led to progressive telomere DNA loss.
- mTert-deficient ES cells exhibited genomic instability, aneuploidy, and telomeric fusions.
- Heterozygous mTert disruption resulted in telomere attrition, distinct from heterozygous mTR cells.
Conclusions:
- Mammalian TERT is sufficient for telomere maintenance.
- Telomere maintenance in mammals relies on a single, limiting TERT component.
- TERT plays a critical role in maintaining genomic stability and preventing telomere dysfunction.