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Molecular and Cellular Biology, March 2007, p. 1592-1601, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01975-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Tetrahymena POT1a Regulates Telomere Length and Prevents Activation of a Cell Cycle Checkpoint

Naduparambil K. Jacob ,^, Rachel Lescasse, Benjamin R. Linger, and Carolyn M. Price^*

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, PO Box 0524, Cincinnati, Ohio 45267-0524

Received 20 October 2006/ Returned for modification 19 November 2006/ Accepted 4 December 2006

The POT1/TEBP telomere proteins are a group of single-stranded DNA (ssDNA)-binding proteins that have long been assumed to protect the G overhang on the telomeric 3' strand. We have found that the Tetrahymena thermophila genome contains two POT1 gene homologs, POT1a and POT1b. The POT1a gene is essential, but POT1b is not. We have generated a conditional POT1a cell line and shown that POT1a depletion results in a monster cell phenotype and growth arrest. However, G-overhang structure is essentially unchanged, indicating that POT1a is not required for overhang protection. In contrast, POT1a is required for telomere length regulation. After POT1a depletion, most telomeres elongate by 400 to 500 bp, but some increase by up to 10 kb. This elongation occurs in the absence of further cell division. The growth arrest caused by POT1a depletion can be reversed by reexpression of POT1a or addition of caffeine. Thus, POT1a is required to prevent a cell cycle checkpoint that is most likely mediated by ATM or ATR (ATM and ATR are protein kinases of the PI-3 protein kinase-like family). Our findings indicate that the essential function of POT1a is to prevent a catastrophic DNA damage response. This response may be activated when nontelomeric ssDNA-binding proteins bind and protect the G overhang.

Published ahead of print on 11 December 2006.

Both authors contributed equally to this work.

Present address: Ohio State University Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210.

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