Previous Article | Next Article 
Molecular and Cellular Biology, January 2005, p. 808-818, Vol. 25, No. 2
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.2.808-818.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro
Colleen Kelleher,
Isabel Kurth, and
Joachim Lingner*
Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland
Received 8 March 2004/
Returned for modification 12 April 2004/
Accepted 18 October 2004
The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the 3' overhanging G-strand DNA and through interaction with the TRF1 duplex telomere DNA binding complex. The influence of POT1 on telomerase activity has not been studied at the molecular level. We show here that POT1 negatively effects telomerase activity in vitro. We find that the DNA binding activity of POT1 is required for telomerase inhibition. Furthermore, POT1 is incapable of inhibiting telomeric repeat addition to substrate primers that are defective for POT1 binding, suggesting that in vivo, POT1 likely affects substrate access to telomerase.
* Corresponding author. Mailing address: ISREC, Chemin des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41-21-692 5912. Fax: 41-21-652 6933. E-mail:
joachim.lingner{at}isrec.ch.
Molecular and Cellular Biology, January 2005, p. 808-818, Vol. 25, No. 2
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.2.808-818.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Kendellen, M. F., Barrientos, K. S., Counter, C. M.
(2009). POT1 Association with TRF2 Regulates Telomere Length. Mol. Cell. Biol.
29: 5611-5619
[Abstract]
[Full Text]
-
Shakirov, E. V., Song, X., Joseph, J. A., Shippen, D. E.
(2009). POT1 proteins in green algae and land plants: DNA-binding properties and evidence of co-evolution with telomeric DNA. Nucleic Acids Res
0: gkp785v1-gkp785
[Abstract]
[Full Text]
-
Esnault, G., Majocchi, S., Martinet, D., Besuchet-Schmutz, N., Beckmann, J. S., Mermod, N.
(2009). Transcription Factor CTF1 Acts as a Chromatin Domain Boundary That Shields Human Telomeric Genes from Silencing. Mol. Cell. Biol.
29: 2409-2418
[Abstract]
[Full Text]
-
Zappulla, D. C., Roberts, J. N., Goodrich, K. J., Cech, T. R., Wuttke, D. S.
(2009). Inhibition of yeast telomerase action by the telomeric ssDNA-binding protein, Cdc13p. Nucleic Acids Res
37: 354-367
[Abstract]
[Full Text]
-
He, H., Wang, Y., Guo, X., Ramchandani, S., Ma, J., Shen, M.-F., Garcia, D. A., Deng, Y., Multani, A. S., You, M. J., Chang, S.
(2009). Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita. Mol. Cell. Biol.
29: 229-240
[Abstract]
[Full Text]
-
Possemato, R., Timmons, J. C., Bauerlein, E. L., Wada, N., Baldwin, A., Masutomi, K., Hahn, W. C.
(2008). Suppression of hPOT1 in Diploid Human Cells Results in an hTERT-Dependent Alteration of Telomere Length Dynamics. Mol Cancer Res
6: 1582-1593
[Abstract]
[Full Text]
-
Okamoto, K., Iwano, T., Tachibana, M., Shinkai, Y.
(2008). Distinct Roles of TRF1 in the Regulation of Telomere Structure and Lengthening. J. Biol. Chem.
283: 23981-23988
[Abstract]
[Full Text]
-
Longhese, M. P.
(2008). DNA damage response at functional and dysfunctional telomeres. Genes Dev.
22: 125-140
[Abstract]
[Full Text]
-
Redon, S., Reichenbach, P., Lingner, J.
(2007). Protein RNA and protein protein interactions mediate association of human EST1A/SMG6 with telomerase. Nucleic Acids Res
35: 7011-7022
[Abstract]
[Full Text]
-
Rossignol, P., Collier, S., Bush, M., Shaw, P., Doonan, J. H.
(2007). Arabidopsis POT1A interacts with TERT-V(I8), an N-terminal splicing variant of telomerase. J. Cell Sci.
120: 3678-3687
[Abstract]
[Full Text]
-
Donigian, J. R., de Lange, T.
(2007). The Role of the Poly(ADP-ribose) Polymerase Tankyrase1 in Telomere Length Control by the TRF1 Component of the Shelterin Complex. J. Biol. Chem.
282: 22662-22667
[Abstract]
[Full Text]
-
Multani, A. S., Chang, S.
(2007). WRN at telomeres: implications for aging and cancer. J. Cell Sci.
120: 713-721
[Abstract]
[Full Text]
-
Jacob, N. K., Lescasse, R., Linger, B. R., Price, C. M.
(2007). Tetrahymena POT1a Regulates Telomere Length and Prevents Activation of a Cell Cycle Checkpoint. Mol. Cell. Biol.
27: 1592-1601
[Abstract]
[Full Text]
-
O'Connor, M. S., Safari, A., Xin, H., Liu, D., Songyang, Z.
(2006). A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc. Natl. Acad. Sci. USA
103: 11874-11879
[Abstract]
[Full Text]
-
Zhang, Q.-S., Manche, L., Xu, R.-M., Krainer, A. R.
(2006). hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA
12: 1116-1128
[Abstract]
[Full Text]
-
Nakamura, M., Nabetani, A., Mizuno, T., Hanaoka, F., Ishikawa, F.
(2005). Alterations of DNA and Chromatin Structures at Telomeres and Genetic Instability in Mouse Cells Defective in DNA Polymerase {alpha}. Mol. Cell. Biol.
25: 11073-11088
[Abstract]
[Full Text]
-
de Lange, T.
(2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev.
19: 2100-2110
[Abstract]
[Full Text]
-
Shakirov, E. V., Surovtseva, Y. V., Osbun, N., Shippen, D. E.
(2005). The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection. Mol. Cell. Biol.
25: 7725-7733
[Abstract]
[Full Text]
-
Zaug, A. J., Podell, E. R., Cech, T. R.
(2005). Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc. Natl. Acad. Sci. USA
102: 10864-10869
[Abstract]
[Full Text]
-
Bunch, J. T., Bae, N. S., Leonardi, J., Baumann, P.
(2005). Distinct Requirements for Pot1 in Limiting Telomere Length and Maintaining Chromosome Stability. Mol. Cell. Biol.
25: 5567-5578
[Abstract]
[Full Text]
-
Moriarty, T. J., Ward, R. J., Taboski, M. A.S., Autexier, C.
(2005). An Anchor Site-Type Defect in Human Telomerase That Disrupts Telomere Length Maintenance and Cellular Immortalization. Mol. Biol. Cell
16: 3152-3161
[Abstract]
[Full Text]
-
Lei, M., Zaug, A. J., Podell, E. R., Cech, T. R.
(2005). Switching Human Telomerase On and Off with hPOT1 Protein in Vitro. J. Biol. Chem.
280: 20449-20456
[Abstract]
[Full Text]