Human CST has independent functions during telomere duplex replication and C-strand fill-in.

Human CST has independent functions during telomere duplex replication and C-strand fill-in.
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DOI:
10.1016/j.celrep.2012.10.007
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发表时间:
2012-11-29
期刊:
影响因子:
8.8
通讯作者:
Price CM
Price CM
中科院分区:
生物学1区
文献类型:
--
作者:
Wang F;Stewart JA;Kasbek C;Zhao Y;Wright WE;Price CM

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Human CST (CTC1-STN1-TEN1) is an RPA-like complex that is needed for efficient replication through the telomere duplex and genome-wide replication restart after fork stalling. Here we show that STN1/CST has a second function in telomere replication during G-overhang maturation. Analysis of overhang structure after STN1 depletion revealed normal kinetics for telomerase-mediated extension in S-phase but a delay in subsequent overhang shortening. This delay resulted from a defect in C-strand fill-in. Short telomeres exhibited the fill-in defect but normal telomere duplex replication, indicating that STN1/CST functions independently in these processes. Our work also indicates that the requirement for STN1/CST in telomere duplex replication correlates with increasing telomere length and replication stress. Our results provide the first direct evidence that STN1/CST participates in C-strand fill-in. They also demonstrate that STN1/CST participates in two mechanistically separate steps during telomere replication and identify CST as a novel replication factor that solves diverse replication-associated problems.
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