• 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

端粒蛋白TRF2调节着着丝粒周围异染色质内的复制起点活性。

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin.

作者信息

Bauwens Serge, Lototska Liudmyla, Koundrioukoff Stephane, Debatisse Michelle, Ye Jing, Gilson Eric, Mendez-Bermudez Aaron

机构信息

Faculty of Medicine Nice, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, Université Côte d'Azur, 06107 Nice, France.

Institut Gustave Roussy, Sorbonne Université, UPMC University, 94805 Villejuif, France.

出版信息

Life (Basel). 2021 Mar 24;11(4):267. doi: 10.3390/life11040267.

DOI:10.3390/life11040267
PMID:33804994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8063955/
Abstract

Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the helicase RTEL1 in order to relieve topological barriers blocking fork progression. Since TRF2 is known to bind the Origin Replication Complex (ORC), we hypothesized that this factor could also play a role at the replication origins (ORI) of these heterochromatin regions. By performing DNA combing analysis, we found that the ORI density is higher within pericentromeric satellite DNA repeats than within bulk genomic DNA and decreased upon TRF2 downregulation. Moreover, we showed that TRF2 and ORC2 interact in pericentromeric DNA, providing a mechanism by which TRF2 is involved in ORI activity. Altogether, our findings reveal an essential role for TRF2 in pericentromeric heterochromatin replication by regulating both replication initiation and elongation.

摘要

由于染色质高度压缩以及重复DNA序列的存在，异染色质区域使得复制过程特别困难。在人类中，通过着丝粒周围异染色质进行复制需要端粒因子TRF2和解旋酶RTEL1形成的复合物结合，以消除阻碍叉状进程的拓扑障碍。由于已知TRF2与复制起始复合物（ORC）结合，我们推测该因子在这些异染色质区域的复制起点（ORI）也可能发挥作用。通过进行DNA梳理分析，我们发现着丝粒周围卫星DNA重复序列中的ORI密度高于基因组总体DNA中的ORI密度，并且在TRF2下调后降低。此外，我们表明TRF2和ORC2在着丝粒周围DNA中相互作用，为TRF2参与ORI活性提供了一种机制。总之，我们的研究结果揭示了TRF2在着丝粒周围异染色质复制中通过调节复制起始和延伸发挥的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/dc287743f103/life-11-00267-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/cbdb8a46e9b1/life-11-00267-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/28071f7e56a2/life-11-00267-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/dc287743f103/life-11-00267-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/cbdb8a46e9b1/life-11-00267-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/28071f7e56a2/life-11-00267-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63e/8063955/dc287743f103/life-11-00267-g003.jpg

相似文献

1
The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin.端粒蛋白TRF2调节着着丝粒周围异染色质内的复制起点活性。
Life (Basel). 2021 Mar 24;11(4):267. doi: 10.3390/life11040267.
2
Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.端粒结合蛋白 TRF2 对异染色质复制的全基因组调控。
Mol Cell. 2018 May 3;70(3):449-461.e5. doi: 10.1016/j.molcel.2018.03.036.
3
TRF2 Mediates Replication Initiation within Human Telomeres to Prevent Telomere Dysfunction.端粒结合因子 2 介导人类端粒内的复制起始以防止端粒功能障碍。
Cell Rep. 2020 Nov 10;33(6):108379. doi: 10.1016/j.celrep.2020.108379.
4
TRF2 recruits ORC through TRFH domain dimerization.TRF2 通过 TRFH 结构域二聚化招募 ORC。
Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):191-201. doi: 10.1016/j.bbamcr.2016.11.004. Epub 2016 Nov 9.
5
Involvement of human ORC and TRF2 in pre-replication complex assembly at telomeres.人类ORC和TRF2参与端粒处复制前复合体的组装。
Genes Cells. 2008 Oct;13(10):1045-59. doi: 10.1111/j.1365-2443.2008.01224.x. Epub 2008 Aug 29.
6
Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats.与端粒结合的TRF1和TRF2会在端粒重复序列处使复制叉停滞。
Nucleic Acids Res. 2004 Mar 8;32(5):1627-37. doi: 10.1093/nar/gkh309. Print 2004.
7
Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence.TP53 激活诱导衰老时的选择性着丝粒异染色质解体。
Nucleic Acids Res. 2022 Jul 22;50(13):7493-7510. doi: 10.1093/nar/gkac603.
8
Origin-dependent initiation of DNA replication within telomeric sequences.端粒序列中依赖起源的 DNA 复制起始。
Nucleic Acids Res. 2010 Jan;38(2):467-76. doi: 10.1093/nar/gkp929. Epub 2009 Nov 11.
9
ORC binding to TRF2 stimulates OriP replication.ORC与TRF2的结合刺激OriP复制。
EMBO Rep. 2006 Jul;7(7):716-21. doi: 10.1038/sj.embor.7400730. Epub 2006 Jun 16.
10
Role of TRF2 in the assembly of telomeric chromatin.端粒重复结合因子2（TRF2）在端粒染色质组装中的作用。
Cell Cycle. 2008 Nov 1;7(21):3461-8. doi: 10.4161/cc.7.21.7013. Epub 2008 Nov 12.

引用本文的文献

1
Chromatin's Influence on Pre-Replication Complex Assembly and Function.染色质对复制前复合体组装及功能的影响。
Biology (Basel). 2024 Feb 27;13(3):152. doi: 10.3390/biology13030152.
2
The nucleolar protein GNL3 prevents resection of stalled replication forks.核仁蛋白 GNL3 防止复制叉停滞的切除。
EMBO Rep. 2023 Dec 6;24(12):e57585. doi: 10.15252/embr.202357585. Epub 2023 Nov 15.
3
MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer.miR-182-3p 靶向 TRF2 并抑制三阴性乳腺癌的肿瘤生长。

本文引用的文献

1
TRF2 Mediates Replication Initiation within Human Telomeres to Prevent Telomere Dysfunction.端粒结合因子 2 介导人类端粒内的复制起始以防止端粒功能障碍。
Cell Rep. 2020 Nov 10;33(6):108379. doi: 10.1016/j.celrep.2020.108379.
2
A predictable conserved DNA base composition signature defines human core DNA replication origins.可预测的保守 DNA 碱基组成特征定义了人类核心 DNA 复制起点。
Nat Commun. 2020 Sep 21;11(1):4826. doi: 10.1038/s41467-020-18527-0.
3
ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization.
EMBO Mol Med. 2023 Jan 11;15(1):e16033. doi: 10.15252/emmm.202216033. Epub 2022 Nov 25.
4
Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence.TP53 激活诱导衰老时的选择性着丝粒异染色质解体。
Nucleic Acids Res. 2022 Jul 22;50(13):7493-7510. doi: 10.1093/nar/gkac603.
5
TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress.端粒复制应激下，TRF2 介导的 ORC 募集是端粒稳定的基础。
Nucleic Acids Res. 2021 Dec 2;49(21):12234-12251. doi: 10.1093/nar/gkab1004.
6
The Intra- and Extra-Telomeric Role of TRF2 in the DNA Damage Response.TRF2在DNA损伤应答中的端粒内和端粒外作用
Int J Mol Sci. 2021 Sep 14;22(18):9900. doi: 10.3390/ijms22189900.
7
Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition.端粒盖帽蛋白复合物的多功能性由其蛋白质组成的变化来解释。
Cells. 2021 Jul 11;10(7):1753. doi: 10.3390/cells10071753.
ORCA/LRWD1通过调节异染色质组织来调控ALT端粒处的同源重组。
iScience. 2020 May 22;23(5):101038. doi: 10.1016/j.isci.2020.101038. Epub 2020 Apr 18.
4
Heterochromatin replication goes hand in hand with telomere protection.异染色质复制与端粒保护齐头并进。
Nat Struct Mol Biol. 2020 Apr;27(4):313-318. doi: 10.1038/s41594-020-0400-1. Epub 2020 Mar 30.
5
Heterochromatin: Guardian of the Genome.异染色质：基因组的守护者。
Annu Rev Cell Dev Biol. 2018 Oct 6;34:265-288. doi: 10.1146/annurev-cellbio-100617-062653. Epub 2018 Jul 25.
6
Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.端粒结合蛋白 TRF2 对异染色质复制的全基因组调控。
Mol Cell. 2018 May 3;70(3):449-461.e5. doi: 10.1016/j.molcel.2018.03.036.
7
The BUB3-BUB1 Complex Promotes Telomere DNA Replication.BUB3-BUB1 复合物促进端粒 DNA 复制。
Mol Cell. 2018 May 3;70(3):395-407.e4. doi: 10.1016/j.molcel.2018.03.032.
8
TRF2 recruits ORC through TRFH domain dimerization.TRF2 通过 TRFH 结构域二聚化招募 ORC。
Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):191-201. doi: 10.1016/j.bbamcr.2016.11.004. Epub 2016 Nov 9.
9
Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers.ORC结合位点的选择性及其与复制时间、脆性位点和癌症中缺失的关系。
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4810-9. doi: 10.1073/pnas.1609060113. Epub 2016 Jul 19.
10
Taz1-Shelterin Promotes Facultative Heterochromatin Assembly at Chromosome-Internal Sites Containing Late Replication Origins.Taz1-保护素促进在含有晚期复制起点的染色体内部位点组装兼性异染色质。
Mol Cell. 2016 Jun 16;62(6):862-874. doi: 10.1016/j.molcel.2016.04.034. Epub 2016 Jun 2.