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Molecular and Cellular Biology, May 2003, p. 3031-3042, Vol. 23, No. 9
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.9.3031-3042.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Replication Proteins Influence the Maintenance of Telomere Length and Telomerase Protein Stability
Maria Dahlén,1,2 Per Sunnerhagen,2 and Teresa S.-F. Wang1*
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324,1
Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University, S-405 30 Göteborg, Sweden2
Received 25 July 2002/
Returned for modification 9 September 2002/
Accepted 9 February 2003
We investigated the effects of fission yeast replication genes on telomere length maintenance and identified 20 mutant alleles that confer lengthening or shortening of telomeres. The telomere elongation was telomerase dependent in the replication mutants analyzed. Furthermore, the telomerase catalytic subunit, Trt1, and the principal initiation and lagging-strand synthesis DNA polymerase, Pol
, were reciprocally coimmunoprecipitated, indicating these proteins physically coexist as a complex in vivo. In a pol
mutant that exhibited abnormal telomere lengthening and slightly reduced telomere position effect, the cellular level of the Trt1 protein was significantly lower and the coimmunoprecipitation of Trt1 and Pol
was severely compromised compared to those in the wild-type pol
cells. Interestingly, ectopic expression of wild-type pol
in this pol
mutant restored the cellular Trt1 protein to the wild-type level and shortened the telomeres to near-wild-type length. These results suggest that there is a close physical relationship between the replication and telomerase complexes. Thus, mutation of a component of the replication complex can affect the telomeric complex in maintaining both telomere length equilibrium and telomerase protein stability.
* Corresponding author. Mailing address: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324. Phone: (650) 725-4907. Fax: (650) 725-6902. E-mail: twang{at}cmgm.stanford.edu.
Molecular and Cellular Biology, May 2003, p. 3031-3042, Vol. 23, No. 9
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.9.3031-3042.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.