Tetrahymena POT1a regulates telomere length and prevents activation of a cell cycle checkpoint.
Jacob NK, Lescasse R, Linger BR, Price CM
Molecular and Cellular Biology (2006)
Category: telomere ¤ Added: Dec 21, 2006 ¤ Rating: ◊◊
The POT1/TEBP telomere proteins are a group of single-strand DNA-binding proteins that have long been assumed to protect the G-overhang on the telomeric 3' strand. We have found that the Tetrahymena genome contains two POT1 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 400-500 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 re-expression 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. Our findings indicate that the essential function of POT1a is to prevent a catastrophic DNA damage response. This response may be activated when non-telomeric ssDNA binding proteins bind and protect the G-overhang.