• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Ku 的 DNA 末端结合活性丧失通过使端粒结合的 Est1 不稳定而非改变 TLC1 稳态来影响端粒长度。

Loss of Ku's DNA end binding activity affects telomere length via destabilizing telomere-bound Est1 rather than altering TLC1 homeostasis.

机构信息

Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, 77030, USA.

Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.

出版信息

Sci Rep. 2019 Jul 23;9(1):10607. doi: 10.1038/s41598-019-46840-2.

DOI:10.1038/s41598-019-46840-2
PMID:31337791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6650470/
Abstract

Saccharomyces cerevisiae telomerase, which maintains telomere length, is comprised of an RNA component, TLC1, the reverse transcriptase, Est2, and regulatory subunits, including Est1. The Yku70/Yku80 (Ku) heterodimer, a DNA end binding (DEB) protein, also contributes to telomere length maintenance. Ku binds TLC1 and telomere ends in a mutually exclusive fashion, and is required to maintain levels and nuclear localization of TLC1. Ku also interacts with Sir4, which localizes to telomeres. Here we sought to determine the role of Ku's DEB activity in telomere length maintenance by utilizing yku70-R456E mutant strains, in which Ku has reduced DEB and telomere association but proficiency in TLC1 and Sir4 binding, and TLC1 nuclear retention. Telomere lengths in a yku70-R456E strain were nearly as short as those in yku∆ strains and shorter than in strains lacking either Sir4, Ku:Sir4 interaction, or Ku:TLC1 interaction. TLC1 levels were decreased in the yku70-R456E mutant, yet overexpression of TLC1 failed to restore telomere length. Reduced DEB activity did not impact Est1's ability to associate with telomerase but did result in decreased association of Est1 with the telomere. These findings suggest Ku's DEB activity maintains telomere length homeostasis by preserving Est1's interaction at the telomere rather than altering TLC1 levels.

摘要

酿酒酵母端粒酶可维持端粒长度，由 RNA 组分 TLC1、逆转录酶 Est2 和调节亚基（包括 Est1）组成。Yku70/Yku80（Ku）异二聚体是一种 DNA 末端结合（DEB）蛋白，也有助于维持端粒长度。Ku 以相互排斥的方式结合 TLC1 和端粒末端，并且需要维持 TLC1 的水平和核定位。Ku 还与定位于端粒的 Sir4 相互作用。在这里，我们试图通过利用 yku70-R456E 突变株来确定 Ku 的 DEB 活性在维持端粒长度中的作用，在该突变株中，Ku 的 DEB 和与端粒的结合减少，但在结合 TLC1 和 Sir4 以及保留 TLC1 核方面仍保持高效。yku70-R456E 菌株的端粒长度几乎与 yku∆菌株一样短，比缺乏 Sir4、Ku：Sir4 相互作用或 Ku：TLC1 相互作用的菌株更短。yku70-R456E 突变体中的 TLC1 水平降低，但过量表达 TLC1 未能恢复端粒长度。降低的 DEB 活性并没有影响 Est1 与端粒酶结合的能力，但确实导致 Est1 与端粒的结合减少。这些发现表明，Ku 的 DEB 活性通过保持 Est1 在端粒上的相互作用而不是改变 TLC1 水平来维持端粒长度的动态平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/2edc1852f6b1/41598_2019_46840_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/7eb48c9db2a7/41598_2019_46840_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/0786c08579a0/41598_2019_46840_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/73640b87f97a/41598_2019_46840_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/1935cf63dfc9/41598_2019_46840_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/72909882bd49/41598_2019_46840_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/0255abaa2354/41598_2019_46840_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/2edc1852f6b1/41598_2019_46840_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/7eb48c9db2a7/41598_2019_46840_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/0786c08579a0/41598_2019_46840_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/73640b87f97a/41598_2019_46840_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/1935cf63dfc9/41598_2019_46840_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/72909882bd49/41598_2019_46840_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/0255abaa2354/41598_2019_46840_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e919/6650470/2edc1852f6b1/41598_2019_46840_Fig7_HTML.jpg

相似文献

1
Loss of Ku's DNA end binding activity affects telomere length via destabilizing telomere-bound Est1 rather than altering TLC1 homeostasis.Ku 的 DNA 末端结合活性丧失通过使端粒结合的 Est1 不稳定而非改变 TLC1 稳态来影响端粒长度。
Sci Rep. 2019 Jul 23;9(1):10607. doi: 10.1038/s41598-019-46840-2.
2
The principal role of Ku in telomere length maintenance is promotion of Est1 association with telomeres.Ku在端粒长度维持中的主要作用是促进Est1与端粒的结合。
Genetics. 2014 Aug;197(4):1123-36. doi: 10.1534/genetics.114.164707. Epub 2014 May 30.
3
Ku must load directly onto the chromosome end in order to mediate its telomeric functions.Ku 必须直接加载到染色体末端，才能介导其端粒功能。
PLoS Genet. 2011 Aug;7(8):e1002233. doi: 10.1371/journal.pgen.1002233. Epub 2011 Aug 11.
4
Suppression of telomere capping defects of Saccharomyces cerevisiae yku70 and yku80 mutants by telomerase.端粒酶抑制酿酒酵母 yku70 和 yku80 突变体的端粒帽缺陷。
G3 (Bethesda). 2021 Dec 8;11(12). doi: 10.1093/g3journal/jkab359.
5
Mutually exclusive binding of telomerase RNA and DNA by Ku alters telomerase recruitment model.端粒酶 RNA 和 DNA 与 Ku 的互斥结合改变了端粒酶募集模型。
Cell. 2012 Mar 2;148(5):922-32. doi: 10.1016/j.cell.2012.01.033. Epub 2012 Feb 23.
6
Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends.Ku与端粒酶RNA相互作用，以促进在天然和断裂染色体末端添加端粒。
Genes Dev. 2003 Oct 1;17(19):2384-95. doi: 10.1101/gad.1125903. Epub 2003 Sep 15.
7
Structural Insights into Yeast Telomerase Recruitment to Telomeres.酵母端粒酶招募到端粒的结构见解。
Cell. 2018 Jan 11;172(1-2):331-343.e13. doi: 10.1016/j.cell.2017.12.008. Epub 2017 Dec 28.
8
Ku DNA End-Binding Activity Promotes Repair Fidelity and Influences End-Processing During Nonhomologous End-Joining in .Ku DNA 结合活性促进非同源末端连接修复的保真度并影响末端加工。
Genetics. 2018 May;209(1):115-128. doi: 10.1534/genetics.117.300672. Epub 2018 Mar 2.
9
Telomerase subunit overexpression suppresses telomere-specific checkpoint activation in the yeast yku80 mutant.端粒酶亚基过表达抑制酵母yku80突变体中端粒特异性检查点的激活。
EMBO Rep. 2001 Mar;2(3):197-202. doi: 10.1093/embo-reports/kve038.
10
Ku can contribute to telomere lengthening in yeast at multiple positions in the telomerase RNP.Ku 可以在端粒酶 RNP 的多个位置促进酵母中的端粒延长。
RNA. 2011 Feb;17(2):298-311. doi: 10.1261/rna.2483611. Epub 2010 Dec 21.

引用本文的文献

1
Targeting DNA damage sensors for cancer therapy.靶向DNA损伤传感器用于癌症治疗。
DNA Repair (Amst). 2025 May;149:103841. doi: 10.1016/j.dnarep.2025.103841. Epub 2025 May 2.
2
Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks.Ku-DNA结合抑制剂可调节对DNA双链断裂的DNA损伤反应。
NAR Cancer. 2023 Feb 6;5(1):zcad003. doi: 10.1093/narcan/zcad003. eCollection 2023 Mar.
3
Telomere biology disorders.端粒生物学紊乱

本文引用的文献

1
Shelterin-Mediated Telomere Protection.端粒保护的庇护体机制。
Annu Rev Genet. 2018 Nov 23;52:223-247. doi: 10.1146/annurev-genet-032918-021921. Epub 2018 Sep 12.
2
Structural Insights into Yeast Telomerase Recruitment to Telomeres.酵母端粒酶招募到端粒的结构见解。
Cell. 2018 Jan 11;172(1-2):331-343.e13. doi: 10.1016/j.cell.2017.12.008. Epub 2017 Dec 28.
3
Consider the workhorse: Nonhomologous end-joining in budding yeast.以主力军为例：芽殖酵母中的非同源末端连接。
NPJ Genom Med. 2021 May 28;6(1):36. doi: 10.1038/s41525-021-00198-5.
4
Genome stability is guarded by yeast Rtt105 through multiple mechanisms.酵母 Rtt105 通过多种机制来保护基因组稳定性。
Genetics. 2021 Feb 9;217(2). doi: 10.1093/genetics/iyaa035.
5
Telomerase, the recombination machinery and Rap1 play redundant roles in yeast telomere protection.端粒酶、重组机制和 Rap1 在酵母端粒保护中发挥冗余作用。
Curr Genet. 2021 Feb;67(1):153-163. doi: 10.1007/s00294-020-01125-4. Epub 2020 Nov 6.
Biochem Cell Biol. 2016 Oct;94(5):396-406. doi: 10.1139/bcb-2016-0001. Epub 2016 Mar 31.
4
The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae.端粒酶的Ku亚基与Sir4结合，以招募端粒酶来延长酿酒酵母中的端粒。
Elife. 2015 Jul 28;4:e07750. doi: 10.7554/eLife.07750.
5
Regulated assembly and disassembly of the yeast telomerase quaternary complex.酵母端粒酶四元复合物的调控组装与拆卸
Genes Dev. 2014 Oct 1;28(19):2077-89. doi: 10.1101/gad.246256.114. Epub 2014 Sep 19.
6
The principal role of Ku in telomere length maintenance is promotion of Est1 association with telomeres.Ku在端粒长度维持中的主要作用是促进Est1与端粒的结合。
Genetics. 2014 Aug;197(4):1123-36. doi: 10.1534/genetics.114.164707. Epub 2014 May 30.
7
Biology of telomeres: lessons from budding yeast.端粒生物学：芽殖酵母的启示。
FEMS Microbiol Rev. 2014 Mar;38(2):144-71. doi: 10.1111/1574-6976.12054.
8
TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres.TRF2 与 Ku 异源四聚体界面的相互作用为理解人端粒处 c-NHEJ 的预防提供了线索。
Cell Rep. 2013 Oct 17;5(1):194-206. doi: 10.1016/j.celrep.2013.08.040. Epub 2013 Oct 3.
9
Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: beginning to end.关于酿酒酵母端粒的一切你想知道的：从开始到结束。
Genetics. 2012 Aug;191(4):1073-105. doi: 10.1534/genetics.111.137851.
10
Mutually exclusive binding of telomerase RNA and DNA by Ku alters telomerase recruitment model.端粒酶 RNA 和 DNA 与 Ku 的互斥结合改变了端粒酶募集模型。
Cell. 2012 Mar 2;148(5):922-32. doi: 10.1016/j.cell.2012.01.033. Epub 2012 Feb 23.