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分生组织紊乱 1 编码 TEN1,这是一种必需的端粒蛋白,可调节拟南芥中端粒酶的进程。

MERISTEM DISORGANIZATION1 encodes TEN1, an essential telomere protein that modulates telomerase processivity in Arabidopsis.

机构信息

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.

出版信息

Plant Cell. 2013 Apr;25(4):1343-54. doi: 10.1105/tpc.112.107425. Epub 2013 Apr 9.

DOI:10.1105/tpc.112.107425
PMID:23572541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3663272/
Abstract

Telomeres protect chromosome ends from being recognized as DNA damage, and they facilitate the complete replication of linear chromosomes. CST [for CTC1(Cdc13)/STN1/TEN1] is a trimeric chromosome end binding complex implicated in both aspects of telomere function. Here, we characterize TEN1 in the flowering plant Arabidopsis thaliana. We report that TEN1 (for telomeric pathways in association with Stn1, which stands for suppressor of cdc thirteen) is encoded by a previously characterized gene, MERISTEM DISORGANIZATION1 (MDO1). A point mutation in MDO1, mdo1-1/ten1-3 (G77E), triggers stem cell differentiation and death as well as a constitutive DNA damage response. We provide biochemical and genetic evidence that ten1-3 is likely to be a null mutation. As with ctc1 and stn1 null mutants, telomere tracts in ten1-3 are shorter and more heterogeneous than the wild type. Mutants also exhibit frequent telomere fusions, increased single-strand telomeric DNA, and telomeric circles. However, unlike stn1 or ctc1 mutants, telomerase enzyme activity is elevated in ten1-3 mutants due to an increase in repeat addition processivity. In addition, TEN1 is detected at a significantly smaller fraction of telomeres than CTC1. These data indicate that TEN1 is critical for telomere stability and also plays an unexpected role in modulating telomerase enzyme activity.

摘要

端粒保护染色体末端不被识别为 DNA 损伤,并促进线性染色体的完全复制。CST[代表 CTC1(Cdc13)/STN1/TEN1]是一种三聚体染色体末端结合复合物,涉及端粒功能的两个方面。在这里,我们对拟南芥中的 TEN1 进行了研究。我们报告称,TEN1(代表与 STN1 相关的端粒途径,STN1 代表 cdc 十三的抑制因子)是由一个先前被表征的基因 MERISTEM DISORGANIZATION1(MDO1)编码的。MDO1 中的一个点突变,mdo1-1/ten1-3(G77E),触发干细胞分化和死亡以及组成型 DNA 损伤反应。我们提供了生化和遗传证据,表明 ten1-3 很可能是一个无效突变。与 ctc1 和 stn1 缺失突变体一样,ten1-3 中的端粒片段比野生型更短且更不均匀。突变体还表现出频繁的端粒融合、增加的单链端粒 DNA 和端粒环。然而,与 stn1 或 ctc1 突变体不同,ten1-3 突变体中的端粒酶酶活性由于重复添加过程的增加而升高。此外,TEN1 在端粒上的检测比例明显小于 CTC1。这些数据表明 TEN1 对端粒稳定性至关重要,并且还在调节端粒酶酶活性方面发挥了意想不到的作用。

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MERISTEM DISORGANIZATION1 encodes TEN1, an essential telomere protein that modulates telomerase processivity in Arabidopsis.分生组织紊乱 1 编码 TEN1,这是一种必需的端粒蛋白,可调节拟南芥中端粒酶的进程。
Plant Cell. 2013 Apr;25(4):1343-54. doi: 10.1105/tpc.112.107425. Epub 2013 Apr 9.
2
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STN1 protects chromosome ends in Arabidopsis thaliana.STN1保护拟南芥中的染色体末端。
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本文引用的文献

1
Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.全基因组荟萃分析表明 CTC1 和 ZNF676 是调节人类端粒动态平衡的基因。
Hum Mol Genet. 2012 Dec 15;21(24):5385-94. doi: 10.1093/hmg/dds382. Epub 2012 Sep 21.
2
Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in.人类 Stn1 通过促进端粒上有效滞后链合成和介导 C 链填充来保护端粒完整性。
Cell Res. 2012 Dec;22(12):1681-95. doi: 10.1038/cr.2012.132. Epub 2012 Sep 11.
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Mutations in the telomere capping complex in bone marrow failure and related syndromes.骨髓衰竭及其相关综合征中端粒加帽复合物的突变。
Haematologica. 2013 Mar;98(3):334-8. doi: 10.3324/haematol.2012.071068. Epub 2012 Aug 16.
4
Human CST promotes telomere duplex replication and general replication restart after fork stalling.人类 CST 促进端粒双链复制,并在叉停滞后促进普遍复制重启动。
EMBO J. 2012 Aug 29;31(17):3537-49. doi: 10.1038/emboj.2012.215. Epub 2012 Aug 3.
5
Blunt-ended telomeres: an alternative ending to the replication and end protection stories.钝端端粒:复制和末端保护故事的另一种结局。
Genes Dev. 2012 Aug 1;26(15):1648-52. doi: 10.1101/gad.199059.112.
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Chromosome end protection by blunt-ended telomeres.端粒的钝端保护染色体末端。
Genes Dev. 2012 Aug 1;26(15):1703-13. doi: 10.1101/gad.194944.112. Epub 2012 Jul 18.
7
The human CST complex is a terminator of telomerase activity.人类 CST 复合物是端粒酶活性的终结者。
Nature. 2012 Aug 23;488(7412):540-4. doi: 10.1038/nature11269.
8
Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST.端粒 3'突出端来源于 Exo1 和 Apollo 的酶切,并用 POT1b 相关的 CST 进行填补。
Cell. 2012 Jul 6;150(1):39-52. doi: 10.1016/j.cell.2012.05.026. Epub 2012 Jun 28.
9
CTC1 Mutations in a patient with dyskeratosis congenita.先天性角化不良患者的 CTC1 突变。
Pediatr Blood Cancer. 2012 Aug;59(2):311-4. doi: 10.1002/pbc.24193. Epub 2012 Apr 24.
10
CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion.CTC1 缺失导致端粒复制缺陷,导致灾难性的端粒丢失和干细胞耗竭。
EMBO J. 2012 May 16;31(10):2309-21. doi: 10.1038/emboj.2012.96. Epub 2012 Apr 24.