RPA-like Mammalian Ctc1-Stn1-Ten1 Complex Binds to Single-Stranded DNA and Protects Telomeres Independently of the Pot1 Pathway
RPA-like Mammalian Ctc1-Stn1-Ten1 Complex Binds to Single-Stranded DNA and Protects Telomeres Independently of the Pot1 Pathway
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DOI：
10.1016/j.molcel.2009.08.009
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发表时间：
2009-10-23
期刊：
影响因子：
16
通讯作者：
Ishikawa, Fuyuki
中科院分区：
文献类型：
--
作者：
Miyake, Yasuyuki;Nakamura, Mirai;Ishikawa, Fuyuki
芽殖酵母Cdc 13、Stn 1和Ten 1形成CST复合物以保护端粒免受致命的DNA降解。目前尚不清楚类似的复合体是否在高等真核生物中保守。在这里，我们分离了哺乳动物STN 1和TEN 1同源物和CTC 1（保守的端粒维持组分1）。这三种蛋白含有推定的OB-折叠结构域，并形成称为CST的复合物，其以不依赖于序列的方式以高亲和力结合单链DNA。CST与端粒的一部分始终在细胞周期中，在静止细胞和Pot 1敲低细胞。在S期不与复制灶共定位。在Stn 1敲低细胞中观察到单链G链端粒DNA丰度的显着增加。我们建议，CST是一个复制蛋白A（RPA）样复合物，不直接参与传统的DNA复制叉，但在DNA代谢中发挥作用，经常需要端粒。
Budding yeast Cdc13, Stn1, and Ten1 form the CST complex to protect telomeres from lethal DNA degradation. It remains unknown whether similar complexes are conserved in higher eukaryotes or not. Here we isolated mammalian STN1 and TEN1 homologs and CTC1 (conserved telomere maintenance component 1). The three proteins contain putative OB-fold domains and form a complex called CST, which binds to single-stranded DNA with high affinity in a sequence-independent manner. CST associates with a fraction of telomeres consistently during the cell cycle, in quiescent cells and Pot1-knockdown cells. It does not colocalize with replication foci in S phase. Significant increases in the abundance of single-stranded G-strand telomeric DNA were observed in Stn1-knockdown cells. We propose that CST is a replication protein A (RPA)-like complex that is not directly involved in conventional DNA replication at forks but plays a role in DNA metabolism frequently required by telomeres.