Pol α-primase dependent nuclear localization of the mammalian CST complex.
Pol α-primase dependent nuclear localization of the mammalian CST complex.
复制标题
DOI：
10.1038/s42003-021-01845-4
复制
发表时间：
2021-03-17
影响因子：
5.9
通讯作者：
Skordalakes E
中科院分区：
文献类型：
--
作者：
Kelich JM;Papaioannou H;Skordalakes E
由CTC 1、STN 1和TEN 1组成的人类CST复合物在端粒维持和稳态中起关键作用。具体而言，CST通过抑制端粒酶接近端粒突出端来终止端粒延伸，并通过将DNA聚合酶α引发酶（Pol α-引发酶）募集到端粒C链来促进滞后链填充。在这里，我们发现，CST具有动态的细胞内定位，是细胞周期依赖性的。我们报告了DNA复制开始后几小时核CST的增加，随后在有丝分裂前从核中退出。我们鉴定了CTC 1参与Pol α-引发酶结合和核定位的氨基酸。结果表明，CST复合物不含核定位信号（NLS），其核定位依赖于Pol α引发酶。影响CST核输入的亚型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。Kelich，Papaioannou和Skordalakes研究了哺乳动物CST的细胞内定位动力学，CST是一种对端粒维持和稳态至关重要的蛋白质复合物。他们发现CST复合物以细胞周期依赖性的方式定位于细胞核，需要Pol α-引发酶的结合，并且影响其核输入的突变与人类端粒综合征和癌症相关。
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. 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 α-primase and that mutations affecting its nuclear import are associated with human telomere syndromes and cancer.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
14.9
作者：
Bhattacharjee A;Wang Y;Diao J;Price CM
通讯作者：
Price CM
影响因子：
4.5
作者：
Bhattacharjee A;Stewart J;Chaiken M;Price CM
通讯作者：
Price CM
影响因子：
64.8
作者：
Chen, Liuh-Yow;Redon, Sophie;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
1.6
作者：
DelProposto, James;Majmudar, Chinmay Y.;Brown, William Clay
通讯作者：
Brown, William Clay