The human CST complex is a terminator of telomerase activity
Language: 
English
Abstract: 

The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres during the S phase of the cell cycle, and adds ~60 nucleotides in a single round of extension, after which telomerase is turned off by unknown mechanisms. Here we show that the human CST (CTC1, STN1 and TEN1) complex, previously implicated in telomere protection and DNA metabolism, inhibits telomerase activity through primer sequestration and physical interaction with the protection of telomeres 1 (POT1)ñTPP1 telomerase processivity factor. CST competes with POT1ñTPP1 for telomeric DNA, and CSTñtelomeric-DNA binding increases during late S/G2 phase only on telomerase action, coinciding with telomerase shut-off. Depletion of CST allows excessive telomerase activity, promoting telomere elongation. We propose that through binding of the telomerase-extended telomere, CST limits telomerase action at individual telomeres to approximately one binding and extension event per cell cycle. Our findings define the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.

Author(s): 
Chen, Liuh-Yow
Redon, Sophie
Lingner, Joachim
Item Type: 
Journal Article
Publication Title: 
Nature
Journal Abbreviation: 
Nature
Publication Date: 
8/23/2012
Publication Year: 
2012
Pages: 
540-544
Volume: 
488
Issue: 
7412
ISSN: 
1476-4687
DOI: 
10.1038/nature11269
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22763445

Turabian/Chicago Citation

Liuh-Yow Chen, Sophie Redon and Joachim Lingner. 8/23/2012. "The human CST complex is a terminator of telomerase activity." Nature 488: 7412: 540-544. 10.1038/nature11269.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/nature11269 | issn = 1476-4687 | volume = 488 | pages = 540-544 | last = Chen | first = Liuh-Yow | coauthors = Redon, Sophie, Lingner, Joachim | title = The human CST complex is a terminator of telomerase activity | journal = Nature | date = 8/23/2012 | pmid = | pmc = }} </ref>