The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo.
Mammalian telomerase is essential for the maintenance of telomere length [1-5]. Its catalytic core comprises a reverse transcriptase component (TERT) and an RNA component. While the biochemical role of mammalian TERT is well established [6-11], it is unknown whether it is sufficient for telomere-length maintenance, chromosome stability or other cellular processes. Cells from mice in which the mTert gene had been disrupted showed progressive loss of telomere DNA, a phenotype similar to cells in which the gene encoding the telomerase RNA component (mTR) has been disrupted [1,12]. On prolonged growth, mTert-deficient embryonic stem (ES) cells exhibited genomic instability, aneuploidy and telomeric fusions. ES cells heterozygous for the mTert disruption also showed telomere attrition, a phenotype that differs from heterozygous mTR cells [12]. Thus, telomere maintenance in mammals is carried out by a single, limiting TERT.
Liu
Y
Y
Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, 620 University Avenue, ON M5G 2C1, Toronto, Canada.
Snow
B E
BE
Hande
M P
MP
Yeung
D
D
Erdmann
N J
NJ
Wakeham
A
A
Itie
A
A
Siderovski
D P
DP
Lansdorp
P M
PM
Robinson
M O
MO
Harrington
L
L
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins; D018390:Gene Targeting; D051379:Mice; D012313:RNA; D019098:Telomerase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000502:physiology*
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase; C509187:Tert protein, mouse