• 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

人类GINS复合物与Cdc45和MCM相关联，对DNA复制至关重要。

The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.

作者信息

Aparicio Tomás, Guillou Emmanuelle, Coloma Javier, Montoya Guillermo, Méndez Juan

机构信息

DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.

出版信息

Nucleic Acids Res. 2009 Apr;37(7):2087-95. doi: 10.1093/nar/gkp065. Epub 2009 Feb 17.

DOI:10.1093/nar/gkp065
PMID:19223333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2673421/
Abstract

The GINS complex, originally discovered in Saccharomyces cerevisiae and Xenopus laevis, binds to DNA replication origins shortly before the onset of S phase and travels with the replication forks after initiation. In this study we present a detailed characterization of the human GINS (hGINS) homolog. Using new antibodies that allow the detection of endogenous hGINS in cells and tissues, we have examined its expression, abundance, subcellular localization and association with other DNA replication proteins. Expression of hGINS is restricted to actively proliferating cells. During the S phase, hGINS becomes part of a Cdc45-MCM-GINS (CMG) complex that is assembled on chromatin. Down-regulation of hGINS destabilizes CMG, causes a G1-S arrest and slows down ongoing DNA replication, effectively blocking cell proliferation. Our data support the notion that hGINS is an essential component of the human replisome.

摘要

GINS复合体最初是在酿酒酵母和非洲爪蟾中发现的，在S期开始前不久与DNA复制起点结合，并在起始后随复制叉移动。在本研究中，我们对人类GINS（hGINS）同源物进行了详细表征。使用能够检测细胞和组织中内源性hGINS的新抗体，我们检测了其表达、丰度、亚细胞定位以及与其他DNA复制蛋白的关联。hGINS的表达仅限于活跃增殖的细胞。在S期，hGINS成为组装在染色质上的Cdc45-MCM-GINS（CMG）复合体的一部分。hGINS的下调会使CMG不稳定，导致G1-S期阻滞并减缓正在进行的DNA复制，有效阻断细胞增殖。我们的数据支持hGINS是人类复制体重要组成部分的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/b15c43eee526/gkp065f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/3907f23934b3/gkp065f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/e92072ca2518/gkp065f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/1ae948f76be6/gkp065f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/f1701a6eac40/gkp065f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/331e0065ec31/gkp065f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/448bd3bb633d/gkp065f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/b15c43eee526/gkp065f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/3907f23934b3/gkp065f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/e92072ca2518/gkp065f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/1ae948f76be6/gkp065f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/f1701a6eac40/gkp065f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/331e0065ec31/gkp065f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/448bd3bb633d/gkp065f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/b15c43eee526/gkp065f7.jpg

相似文献

1
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.人类GINS复合物与Cdc45和MCM相关联，对DNA复制至关重要。
Nucleic Acids Res. 2009 Apr;37(7):2087-95. doi: 10.1093/nar/gkp065. Epub 2009 Feb 17.
2
Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS.Mcm10 在真核复制 DNA 解旋酶 Cdc45-Mcm-GINS 的功能中发挥作用。
Curr Biol. 2012 Feb 21;22(4):343-9. doi: 10.1016/j.cub.2012.01.023. Epub 2012 Jan 26.
3
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.GINS在真核生物DNA复制叉的复制体进展复合物中维持Cdc45与MCM的结合。
Nat Cell Biol. 2006 Apr;8(4):358-66. doi: 10.1038/ncb1382. Epub 2006 Mar 12.
4
Protein interaction and cellular localization of human CDC45.人 CDC45 的蛋白相互作用和细胞定位。
J Biochem. 2013 Apr;153(4):381-8. doi: 10.1093/jb/mvt004. Epub 2013 Jan 30.
5
Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM.Cdc45和GINS的古菌直系同源物形成一个稳定的复合物，该复合物可刺激MCM的解旋酶活性。
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13390-13395. doi: 10.1073/pnas.1613825113. Epub 2016 Nov 7.
6
Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks.Sld3和GINS在真核生物DNA复制叉的建立与推进过程中的不同作用。
EMBO J. 2006 Apr 19;25(8):1753-63. doi: 10.1038/sj.emboj.7601063. Epub 2006 Apr 6.
7
GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication.GINS复合体蛋白Sld5在DNA复制过程中招募SIK1以激活MCM解旋酶。
Cell Signal. 2016 Dec;28(12):1852-1862. doi: 10.1016/j.cellsig.2016.08.018. Epub 2016 Aug 31.
8
Dpb2 integrates the leading-strand DNA polymerase into the eukaryotic replisome.Dpb2 将领头链 DNA 聚合酶整合到真核复制体中。
Curr Biol. 2013 Apr 8;23(7):543-52. doi: 10.1016/j.cub.2013.02.011. Epub 2013 Mar 14.
9
Structure of human Cdc45 and implications for CMG helicase function.人 Cdc45 结构及其对 CMG 解旋酶功能的影响。
Nat Commun. 2016 May 18;7:11638. doi: 10.1038/ncomms11638.
10
GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding.GINS 和 Sld3 竞争 Mcm2-7 和 Cdc45 的结合。
J Biol Chem. 2011 Apr 22;286(16):14157-67. doi: 10.1074/jbc.M111.218305. Epub 2011 Mar 1.

引用本文的文献

1
Induction of the human gene promoter activity by natural compound ‑resveratrol.天然化合物白藜芦醇诱导人基因启动子活性。
Mol Med Rep. 2024 Jun;29(6). doi: 10.3892/mmr.2024.13216. Epub 2024 Apr 5.
2
miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication.miR-28 为基础的联合治疗通过重编 DNA 复制来抑制侵袭性 B 细胞淋巴瘤的生长。
Cell Death Dis. 2023 Oct 18;14(10):687. doi: 10.1038/s41419-023-06178-0.
3
H4S47 O-GlcNAcylation regulates the activation of mammalian replication origins.

本文引用的文献

1
Replication licensing and cancer--a fatal entanglement?复制许可与癌症——致命的纠缠？
Nat Rev Cancer. 2008 Oct;8(10):799-806. doi: 10.1038/nrc2500. Epub 2008 Aug 29.
2
A chemical method for fast and sensitive detection of DNA synthesis in vivo.一种用于体内DNA合成快速灵敏检测的化学方法。
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2415-20. doi: 10.1073/pnas.0712168105. Epub 2008 Feb 12.
3
Crystal structure of the GINS complex and functional insights into its role in DNA replication.GINS复合物的晶体结构及其在DNA复制中作用的功能见解。
H4S47 O-GlcNAcylation 调控哺乳动物复制起始点的激活。
Nat Struct Mol Biol. 2023 Jun;30(6):800-811. doi: 10.1038/s41594-023-00998-6. Epub 2023 May 18.
4
Identification of novel key genes associated with uterine corpus endometrial carcinoma progression and prognosis.鉴定与子宫内膜癌进展和预后相关的新型关键基因。
Ann Transl Med. 2023 Jan 31;11(2):100. doi: 10.21037/atm-22-6461.
5
Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.解析 CMG 解旋酶在先天性免疫缺陷中的作用。
J Clin Immunol. 2023 Jul;43(5):847-861. doi: 10.1007/s10875-023-01437-3. Epub 2023 Feb 21.
6
Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia.GINS4 部分功能丧失突变导致 NK 细胞缺陷伴中性粒细胞减少症。
JCI Insight. 2022 Nov 8;7(21):e154948. doi: 10.1172/jci.insight.154948.
7
Multi-omics data integration for subtype identification of Chinese lower-grade gliomas: A joint similarity network fusion approach.基于多组学数据整合的中国低级别胶质瘤亚型鉴定：联合相似性网络融合方法
Comput Struct Biotechnol J. 2022 Jul 2;20:3482-3492. doi: 10.1016/j.csbj.2022.06.065. eCollection 2022.
8
Multiple RNA virus matrix proteins interact with SLD5 to manipulate host cell cycle.多种 RNA 病毒基质蛋白与 SLD5 相互作用以操纵宿主细胞周期。
J Gen Virol. 2021 Dec;102(12). doi: 10.1099/jgv.0.001697.
9
Biallelic variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis.双等位基因突变 p.(Arg114Leu) 导致伴有颅缝早闭的 Meier-Gorlin 综合征。
J Med Genet. 2022 Aug;59(8):776-780. doi: 10.1136/jmedgenet-2020-107572. Epub 2021 Aug 5.
10
Mitochondria's Role in the Maintenance of Cancer Stem Cells in Glioblastoma.线粒体在胶质母细胞瘤癌干细胞维持中的作用
Front Oncol. 2021 Feb 22;11:582694. doi: 10.3389/fonc.2021.582694. eCollection 2021.
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12685-90. doi: 10.1073/pnas.0705558104. Epub 2007 Jul 25.
4
Cell cycle regulation of DNA replication.DNA复制的细胞周期调控
Annu Rev Genet. 2007;41:237-80. doi: 10.1146/annurev.genet.41.110306.130308.
5
Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.全面的肿瘤细胞系表达谱分析鉴定出黑色素瘤进展的分子特征。
PLoS One. 2007 Jul 4;2(7):e594. doi: 10.1371/journal.pone.0000594.
6
Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase.在S期，人类Cdc45与Mcm2 - 7复合物、GINS复合物以及DNA聚合酶δ和ε之间的相互作用。
Genes Cells. 2007 Jun;12(6):745-58. doi: 10.1111/j.1365-2443.2007.01090.x.
7
Molecular architecture of the human GINS complex.人类GINS复合物的分子结构
EMBO Rep. 2007 Jul;8(7):678-84. doi: 10.1038/sj.embor.7401002. Epub 2007 Jun 8.
8
Crystal structure of the human GINS complex.人类GINS复合物的晶体结构。
Genes Dev. 2007 Jun 1;21(11):1316-21. doi: 10.1101/gad.1548107.
9
A key role for the GINS complex at DNA replication forks.GINS复合物在DNA复制叉处的关键作用。
Trends Cell Biol. 2007 Jun;17(6):271-8. doi: 10.1016/j.tcb.2007.04.002. Epub 2007 Apr 30.
10
Structure of the human GINS complex and its assembly and functional interface in replication initiation.人类GINS复合物的结构及其在复制起始中的组装和功能界面。
Nat Struct Mol Biol. 2007 May;14(5):388-96. doi: 10.1038/nsmb1231. Epub 2007 Apr 8.