The Wistar Institute, Philadelphia, PA, USA.
Commun Biol. 2021 Mar 17;4(1):349. doi: 10.1038/s42003-021-01845-4.
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 α-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 α-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 α-primase. Hypomorphic mutations affecting CST nuclear import are associated with telomere syndromes and cancer, emphasizing the important role of this process in health.
人类 CST 复合物由 CTC1、STN1 和 TEN1 组成，对于端粒的维持和内稳态至关重要。具体来说，CST 通过抑制端粒酶进入端粒突出端来终止端粒延伸，并通过招募 DNA 聚合酶α引发酶（Pol α-primase）到端粒 C 链来促进滞后链填充。在这里，我们揭示 CST 具有依赖于细胞周期的动态细胞内定位。我们报道在 DNA 复制开始后几个小时内核 CST 增加，然后在有丝分裂前从核内输出。我们确定了 CTC1 中参与 Pol α-primase 结合和核定位的氨基酸。我们得出结论，CST 复合物不含核定位信号（NLS），并表明其核定位依赖于 Pol α-primase。影响 CST 核输入的功能降低突变与端粒综合征和癌症相关，强调了这一过程在健康中的重要作用。
