Pol α-primase dependent nuclear localization of the mammalian CST complex

The human CST complex composed of CTC1, STN1, and TEN1 is critically involved in telomere maintenance and homeostasis. Specifically, CST terminates telomere extension by inhibiting telomerase access to the telomeric overhang and facilitates lagging strand fill in by recruiting DNA Polymerase alpha primase (Pol alpha -primase) to the telomeric C-strand. Here we reveal that CST has a dynamic intracellular localization that is cell cycle dependent. We report an increase in nuclear CST several hours after the initiation of DNA replication, followed by exit from the nucleus prior to mitosis. We identify amino acids of CTC1 involved in Pol alpha -primase binding and nuclear localization. We conclude, the CST complex does not contain a nuclear localization signal (NLS) and suggest that its nuclear localization is reliant on Pol alpha -primase. Hypomorphic mutations affecting CST nuclear import are associated with telomere syndromes and cancer, emphasizing the important role of this process in health. Kelich, Papaioannou and Skordalakes investigate the intracellular localization dynamics of the mammalian CST, a protein complex critical for telomere maintenance and homeostasis. They find that the CST complex localizes to the nucleus in a cell cycle-dependent manner that requires binding by Pol alpha -primase and that mutations affecting its nuclear import are associated with human telomere syndromes and cancer.

Automated summary

The human CST complex plays a critical role in telomere maintenance and homeostasis, with its dynamic intracellular localization being cell cycle-dependent. The CST complex lacks a nuclear localization signal and relies on Pol alpha-primase for nuclear import. Mutations affecting CST nuclear import are associated with telomere syndromes and cancer, underscoring the importance of this process in health.