The human CST complex is a terminator of telomerase activity.

© 2012 EPFL

© 2012 EPFL

The human CST complex is a terminator of telomerase activity.

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 the group of Prof. Joachim Lingner (ISREC) 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)–TPP1 telomerase processivity factor. They 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. Their findings define the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.

Liuh-Yow Chen, Sophie Redon & Joachim Lingner, Nature (2012) doi:10.1038/nature11269