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-len gth maintenance, chromosome stability or other cellular processes. Cells fr om 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 th e telomerase RNA component (mTR) has been disrupted [1,12]. On prolonged gr owth, mTert-deficient embryonic stem (ES) cells exhibited genomic instabili ty, aneuploidy and telomeric fusions. ES cells heterozygous for the mTert d isruption also showed telomere attrition, a phenotype that differs from het erozygous mTR cells [12]. Thus, telomere maintenance in mammals is carried out by a single, limiting TERT.