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Molecular and Cellular Biology, June 2000, p. 4115-4127, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Telomere Maintenance in Telomerase-Deficient Mouse Embryonic Stem Cells: Characterization of an Amplified Telomeric DNA

Hiroyuki Niida,1,dagger Yoichi Shinkai,2,* M. Prakash Hande,3,Dagger Takehisa Matsumoto,1 Shoko Takehara,4 Makoto Tachibana,2 Mitsuo Oshimura,4 Peter M. Lansdorp,3,5 and Yasuhiro Furuichi1

Agene Research Institute, Kamakura 247-0063,1 Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto 606-8507,2 and Department of Molecular and Cell Genetics, Faculty of Medicine, Tottori University, Yonago 683-8503,4 Japan; Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, British Columbia V5Z 1L3,3 and Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5,5 Canada

Received 27 September 1999/Returned for modification 4 November 1999/Accepted 7 March 2000

Telomere dynamics, chromosomal instability, and cellular viability were studied in serial passages of mouse embryonic stem (ES) cells in which the telomerase RNA (mTER) gene was deleted. These cells lack detectable telomerase activity, and their growth rate was reduced after more than 300 divisions and almost zero after 450 cell divisions. After this growth crisis, survivor cells with a rapid growth rate did emerge. Such survivors were found to maintain functional telomeres in a telomerase-independent fashion. Although telomerase-independent telomere maintenance has been reported for some immortalized mammalian cells, its molecular mechanism has not been elucidated. Characterization of the telomeric structures in one of the survivor mTER-/- cell lines showed amplification of the same tandem arrays of telomeric and nontelomeric sequences at most of the chromosome ends. This evidence implicates cis/trans amplification as one mechanism for the telomerase-independent maintenance of telomeres in mammalian cells.

* Corresponding author. Mailing address: Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin, Kawara-cho, Kyoto 606-8507, Japan. Phone: 81-75-751-3990. Fax: 81-75-751-3991. E-mail: yshinkai{at}virus.kyoto-u.ac.jp.

dagger Present address: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720.

Dagger Present address: Center for Radiological Research, Columbia University, New York, NY 10032.

Molecular and Cellular Biology, June 2000, p. 4115-4127, Vol. 20, No. 11
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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