• 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

活体秀丽隐杆线虫胚胎中复制许可的动力学。

The dynamics of replication licensing in live Caenorhabditis elegans embryos.

机构信息

Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

出版信息

J Cell Biol. 2012 Jan 23;196(2):233-46. doi: 10.1083/jcb.201110080. Epub 2012 Jan 16.

DOI:10.1083/jcb.201110080
PMID:22249291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3265957/
Abstract

Accurate DNA replication requires proper regulation of replication licensing, which entails loading MCM-2-7 onto replication origins. In this paper, we provide the first comprehensive view of replication licensing in vivo, using video microscopy of Caenorhabditis elegans embryos. As expected, MCM-2-7 loading in late M phase depended on the prereplicative complex (pre-RC) proteins: origin recognition complex (ORC), CDC-6, and CDT-1. However, many features we observed have not been described before: GFP-ORC-1 bound chromatin independently of ORC-2-5, and CDC-6 bound chromatin independently of ORC, whereas CDT-1 and MCM-2-7 DNA binding was interdependent. MCM-3 chromatin loading was irreversible, but CDC-6 and ORC turned over rapidly, consistent with ORC/CDC-6 loading multiple MCM-2-7 complexes. MCM-2-7 chromatin loading further reduced ORC and CDC-6 DNA binding. This dynamic behavior creates a feedback loop allowing ORC/CDC-6 to repeatedly load MCM-2-7 and distribute licensed origins along chromosomal DNA. During S phase, ORC and CDC-6 were excluded from nuclei, and DNA was overreplicated in export-defective cells. Thus, nucleocytoplasmic compartmentalization of licensing factors ensures that DNA replication occurs only once.

摘要

准确的 DNA 复制需要对复制许可进行适当的调节，这需要将 MCM-2-7 加载到复制原点上。在本文中，我们使用秀丽隐杆线虫胚胎的视频显微镜，提供了体内复制许可的第一个全面视图。正如预期的那样，MCM-2-7 在晚期 M 期的加载取决于前复制复合物（pre-RC）蛋白：起始识别复合物（ORC）、CDC-6 和 CDT-1。然而，我们观察到的许多特征以前都没有描述过：GFP-ORC-1 与 ORC-2-5 独立地结合染色质，CDC-6 与 ORC 独立地结合染色质，而 CDT-1 和 MCM-2-7 的 DNA 结合是相互依赖的。MCM-3 染色质的加载是不可逆的，但 CDC-6 和 ORC 迅速周转，这与 ORC/CDC-6 加载多个 MCM-2-7 复合物一致。MCM-2-7 染色质的加载进一步降低了 ORC 和 CDC-6 的 DNA 结合。这种动态行为创建了一个反馈回路，允许 ORC/CDC-6 反复加载 MCM-2-7 并将许可的起始点沿染色体 DNA 分布。在 S 期，ORC 和 CDC-6 被排除在核外，在出口缺陷细胞中 DNA 被过度复制。因此，许可因子的核质区室化确保 DNA 复制只发生一次。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/9b1cb83eba3d/JCB_201110080_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/3092202d503e/JCB_201110080_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/0adf571c52c6/JCB_201110080_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/dad6e6af4f54/JCB_201110080_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/beb5424c8f52/JCB_201110080_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/19b9b195368f/JCB_201110080R_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/1f5d83f2e06f/JCB_201110080_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/9b1cb83eba3d/JCB_201110080_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/3092202d503e/JCB_201110080_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/0adf571c52c6/JCB_201110080_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/dad6e6af4f54/JCB_201110080_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/beb5424c8f52/JCB_201110080_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/19b9b195368f/JCB_201110080R_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/1f5d83f2e06f/JCB_201110080_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1734/3265957/9b1cb83eba3d/JCB_201110080_Fig7.jpg

相似文献

1
The dynamics of replication licensing in live Caenorhabditis elegans embryos.活体秀丽隐杆线虫胚胎中复制许可的动力学。
J Cell Biol. 2012 Jan 23;196(2):233-46. doi: 10.1083/jcb.201110080. Epub 2012 Jan 16.
2
MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.MCM 干扰在爪蟾卵提取物中 DNA 复制的许可-可能是 MCM3 的 C 末端区域的作用。
Cell Cycle. 2018;17(4):492-505. doi: 10.1080/15384101.2017.1415681. Epub 2018 Jan 30.
3
Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression.染色质相关降解由UBXN-3/FAF1定义，以保障DNA复制叉的进展。
Nat Commun. 2016 Feb 4;7:10612. doi: 10.1038/ncomms10612.
4
The consequences of differential origin licensing dynamics in distinct chromatin environments.不同染色质环境中差异起源许可动力学的后果。
Nucleic Acids Res. 2022 Sep 23;50(17):9601-9620. doi: 10.1093/nar/gkac003.
5
The Xenopus origin recognition complex is essential for DNA replication and MCM binding to chromatin.非洲爪蟾起源识别复合体对于DNA复制以及MCM与染色质的结合至关重要。
Curr Biol. 1996 Nov 1;6(11):1416-25. doi: 10.1016/s0960-9822(96)00746-4.
6
CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.CDC-48/p97 协调 CDT-1 的降解与 GINS 染色质解离，以确保忠实的 DNA 复制。
Mol Cell. 2011 Oct 7;44(1):85-96. doi: 10.1016/j.molcel.2011.08.028.
7
C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway.秀丽隐杆线虫的CUL-4通过依赖CKI-1的途径促进CDC-6的核输出，从而防止再复制。
Curr Biol. 2007 Jun 5;17(11):966-72. doi: 10.1016/j.cub.2007.04.055. Epub 2007 May 17.
8
A chromatinized origin reduces the mobility of ORC and MCM through interactions and spatial constraint.染色质化起始点通过相互作用和空间限制降低了 ORC 和 MCM 的流动性。
Nat Commun. 2023 Oct 23;14(1):6735. doi: 10.1038/s41467-023-42524-8.
9
Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase.起始许可需要MCM复制解旋酶结合并水解ATP。
Mol Cell. 2014 Sep 4;55(5):666-77. doi: 10.1016/j.molcel.2014.06.034. Epub 2014 Jul 31.
10
The High-Affinity Interaction between ORC and DNA that Is Required for Replication Licensing Is Inhibited by 2-Arylquinolin-4-Amines.2-芳基喹啉-4-胺抑制复制许可所必需的 ORC 与 DNA 之间的高亲和力相互作用。
Cell Chem Biol. 2017 Aug 17;24(8):981-992.e4. doi: 10.1016/j.chembiol.2017.06.019. Epub 2017 Aug 3.

引用本文的文献

1
Functional dissection of the conserved C. elegans LEM-3/ANKLE1 nuclease reveals a crucial requirement for the LEM-like and GIY-YIG domains for DNA bridge processing.对保守的秀丽隐杆线虫LEM-3/ANKLE1核酸酶的功能剖析揭示了LEM样结构域和GIY-YIG结构域在DNA桥处理中的关键需求。
Nucleic Acids Res. 2025 Mar 20;53(6). doi: 10.1093/nar/gkaf265.
2
The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo.复制解旋酶 CMG 在体内不对称细胞分裂过程中细胞命运分歧是必需的。
Nat Commun. 2024 Oct 30;15(1):9399. doi: 10.1038/s41467-024-53715-2.
3
MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing.

本文引用的文献

1
Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos.高 Cdt1 和 geminin 水平的动态相互作用调节早期非洲爪蟾胚胎的 S 期。
Development. 2012 Jan;139(1):63-74. doi: 10.1242/dev.068676. Epub 2011 Nov 17.
2
Geminin escapes degradation in G1 of mouse pluripotent cells and mediates the expression of Oct4, Sox2, and Nanog.Geminin 可逃避小鼠多能细胞 G1 期的降解，并介导 Oct4、Sox2 和 Nanog 的表达。
Curr Biol. 2011 Apr 26;21(8):692-9. doi: 10.1016/j.cub.2011.03.026. Epub 2011 Apr 14.
3
MCM2-7 form double hexamers at licensed origins in Xenopus egg extract.
MCM2-7 加载依赖性 ORC 释放确保了全基因组起始许可。
Nat Commun. 2024 Aug 24;15(1):7306. doi: 10.1038/s41467-024-51538-9.
4
Distinct roles of Arabidopsis ORC1 proteins in DNA replication and heterochromatic H3K27me1 deposition.拟南芥 ORC1 蛋白在 DNA 复制和异染色质 H3K27me1 沉积中的不同作用。
Nat Commun. 2023 Mar 7;14(1):1270. doi: 10.1038/s41467-023-37024-8.
5
Isolation, profiling, and tracking of extracellular vesicle cargo in Caenorhabditis elegans.在秀丽隐杆线虫中细胞外囊泡货物的分离、分析和追踪。
Curr Biol. 2022 May 9;32(9):1924-1936.e6. doi: 10.1016/j.cub.2022.03.005. Epub 2022 Mar 24.
6
= *: A Framework for Investigating the Regulation of Replication Timing.= *: 一种研究复制时间调控的框架。
Genes (Basel). 2022 Jan 28;13(2):249. doi: 10.3390/genes13020249.
7
Molecular determinants of phase separation for DNA replication licensing factors.DNA 复制许可因子相分离的分子决定因素。
Elife. 2021 Dec 24;10:e70535. doi: 10.7554/eLife.70535.
8
The proteome of developing barley anthers during meiotic prophase I.在减数分裂前期 I 中发育的大麦花粉囊中蛋白质组。
J Exp Bot. 2022 Mar 2;73(5):1464-1482. doi: 10.1093/jxb/erab494.
9
RbAp46/48LIN-53 and HAT-1 are required for initial CENP-AHCP-3 deposition and de novo holocentromere formation on artificial chromosomes in Caenorhabditis elegans embryos.RbAp46/48LIN-53 和 HAT-1 对于在秀丽隐杆线虫胚胎的人工染色体上初始 CENP-AHCP-3 的沉积和从头形成全着丝粒至关重要。
Nucleic Acids Res. 2021 Sep 20;49(16):9154-9173. doi: 10.1093/nar/gkab217.
10
The capacity of origins to load MCM establishes replication timing patterns.起点的加载能力建立了复制时间模式。
PLoS Genet. 2021 Mar 25;17(3):e1009467. doi: 10.1371/journal.pgen.1009467. eCollection 2021 Mar.
MCM2-7 在非洲爪蟾卵提取物的许可起始点形成双六聚体。
J Biol Chem. 2011 Apr 1;286(13):11855-64. doi: 10.1074/jbc.M110.199521. Epub 2011 Jan 31.
4
Highly stable loading of Mcm proteins onto chromatin in living cells requires replication to unload.在活细胞中，Mcm 蛋白高度稳定地加载到染色质上需要复制来卸载。
J Cell Biol. 2011 Jan 10;192(1):29-41. doi: 10.1083/jcb.201007111.
5
C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability.秀丽隐杆线虫的 MCM-4 是一种通用的 DNA 复制和检查点组件，在表皮中对生长和存活有特定的要求。
Dev Biol. 2011 Feb 15;350(2):358-69. doi: 10.1016/j.ydbio.2010.12.009. Epub 2010 Dec 10.
6
A monoclonal antibody toolkit for C. elegans.用于秀丽隐杆线虫的单克隆抗体工具包。
PLoS One. 2010 Apr 13;5(4):e10161. doi: 10.1371/journal.pone.0010161.
7
Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins.MCM2-7 解旋酶通过与 Cdc45 和 GINS 蛋白的结合被激活。
Mol Cell. 2010 Jan 29;37(2):247-58. doi: 10.1016/j.molcel.2009.12.030.
8
A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.一个双六聚体 MCM2-7 复合物在真核生物 DNA 复制的许可过程中被加载到起始 DNA 上。
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi: 10.1073/pnas.0911500106. Epub 2009 Nov 12.
9
Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.在DNA复制起点许可过程中，Mcm2-7双六聚体围绕DNA的协同装载。
Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov 5.
10
Factors affecting the diversity of DNA replication licensing control in eukaryotes.影响真核生物中DNA复制许可控制多样性的因素。
Curr Biol. 2009 Mar 24;19(6):530-5. doi: 10.1016/j.cub.2009.02.034. Epub 2009 Mar 12.