Open AccessTetrahymena POT1a Regulates Telomere Length and Prevents Activation of a Cell CycleCheckpoint
Author(s) -
Naduparambil K. Jacob,
Rachel Lescasse,
Benjamin R. Linger,
Carolyn M. Price
Publication year - 2007
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01975-06
Subject(s) - biology , telomere , tetrahymena , microbiology and biotechnology , telomere binding protein , cell division , dna damage , cell cycle , gene , dna , dna binding protein , genetics , cell , transcription factor
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 theTetrahymena 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 thatPOT1a 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 isrequired 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. Thegrowth 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 (ATMand ATR are protein kinases of the PI-3 protein kinase-like family). Our findings indicate that the essential functionof 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.