Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes.

Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes.
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保守的端粒维持成分 1 与 STN1 相互作用并维持高等真核生物中的染色体末端。

DOI:
10.1016/j.molcel.2009.09.017
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发表时间:
2009-10-23
期刊:
影响因子:
16
通讯作者:
Shippen, Dorothy E.
Shippen, Dorothy E.
中科院分区:
生物学1区
文献类型:
--
作者:
Surovtseva, Yulia V.;Churikov, Dmitri;Boltz, Kara A.;Song, Xiangyu;Lamb, Jonathan C.;Warrington, Ross;Leehy, Katherine;Heacock, Michelle;Price, Carolyn M.;Shippen, Dorothy E.

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酵母端粒蛋白Stn1的同源基因存在于植物中,但CDc13/Stn1/Ten1(CST)复合体的其他成分只在真菌中发现。在这里,我们报告了植物和脊椎动物中保守的端粒维持成分1(CTC1)的鉴定。CTc1编码一个∼140 kDa端粒相关蛋白,预测含有多个OB折叠结构域。CTC1缺失的拟南芥突变体表现出严重的端粒去保护表型,伴随着发育缺陷和不育的快速发生。端粒和亚端粒束显著受到侵蚀,染色体末端表现出更多的G-突出、重组和端到端融合。AtCTC1在生理上和基因上都与AtSTN1相互作用。RNAi耗尽人的CTC1会引发DNA损伤反应、染色质桥、G-突起增加和零星的端粒丢失。这些数据表明,CTC1参与了不同物种的端粒维持,并且在多细胞生物体中,端粒的完整性需要一个类似CST的复合体。
Orthologs of the yeast telomere protein Stn1 are present in plants, but other components of the Cdc13/Stn1/Ten1 (CST) complex have only been found in fungi. Here we report the identification of Conserved Telomere maintenance Component 1 (CTC1) in plants and vertebrates. CTC1 encodes an ∼140 kDa telomere-associated protein predicted to contain multiple OB-fold domains. Arabidopsis mutants null for CTC1 display a severe telomere deprotection phenotype accompanied by a rapid onset of developmental defects and sterility. Telomeric and subtelomeric tracts are dramatically eroded, and chromosome ends exhibit increased G-overhangs, recombination, and end-to-end fusions. AtCTC1 both physically and genetically interacts with AtSTN1. Depletion of human CTC1 by RNAi triggers a DNA damage response, chromatin bridges, increased G-overhangs and sporadic telomere loss. These data indicate that CTC1 participates in telomere maintenance in diverse species and that a CST-like complex is required for telomere integrity in multicellular organisms.
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