Nature Genetics
19, 203 - 206 (1998)
doi:10.1038/580
Severe growth defect in mouse cells lacking the telomerase RNA component
Hiroyuki Niida1, Takehisa Matsumoto2, Hideo Satoh1, Mieko Shiwa1, Yoshiki Tokutake2, Yasuhiro Furuichi2
& Yoichi Shinkai1, 31
Nippon Roche Research Center, 200 Kajiwara, Kamakura, 247-8530, Japan. 2
Agene Research Institute, 200 Kajiwara, Kamakura, 247-8530, Japan. 3
Current address: Institute for Virus Research, Kyoto
University, 53 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8397, Japan.
Correspondence should be addressed to Yoichi Shinkai The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA
onto chromosome ends1. Telomere length is maintained, by the
presence of telomerase activity, in the vast majority of primary tumours and
stem cells2,
3, suggesting that telomere maintenance is essential
for cellular immortalization. Recently, the telomerase RNA component in human4 and mouse5 (TERC and Terc, respectively),
a telomerase-associated protein TEP1/TLP1 (refs 6,7) and the human catalytic subunit protein TERT (Refs 8,9) have been identified.
To examine the role of telomerase in telomere maintenance and cellular viability,
we established Terc-deficient embryonic stem (ES) cells. It is known
that telomerase activity is absent in cells from Terc-knockout mice10. Although the study showed that telomere shortening was observed
in the Terc-deficient cells from first to six generation animals, whether
telomerase-dependent telomere maintenance was essential for cellular viability
remained to be elucidated. To address this issue, we examined Terc-deficient
ES cells under long-term culture conditions. Accompanying the continual telomere
shortening, the growth rate of Terc-deficient ES cells was gradually
reduced after more than 300 divisions. An impaired growth rate was maintained
to approximately 450 divisions, and then cell growth virtually stopped. These
data clearly show that telomerase-dependent telomere maintenance is critical
for the growth of mammalian cells.
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