• 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

TRIM28-HSP90B1 复合物在复制叉上促进 CMG 解旋酶的保留，以确保干细胞基因组的稳定性和胚胎发生。

-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis.

机构信息

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

出版信息

Sci Adv. 2023 Jan 27;9(4):eadf6277. doi: 10.1126/sciadv.adf6277.

DOI:10.1126/sciadv.adf6277
PMID:36706191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9882984/
Abstract

Replication stress is a major source of endogenous DNA damage. Despite the identification of numerous proteins on replication forks to modulate fork or replication machinery activities, it remains unexplored whether noncoding RNAs can localize on stalled forks and play critical regulatory roles. Here, we identify an uncharacterized long noncoding RNA NONMMUT028956 ( for short) predominantly expressed in mouse embryonic stem cells. is accumulated on replication forks to prevent fork collapse and preserve genomic stability and is essential for mouse embryogenesis. Mechanistically, it drives assembly of the -TRIM28-HSP90B1 complex on stalled forks in an interdependent manner downstream of ataxia telangiectasia and Rad3-related (ATR) signaling. -TRIM28-HSP90B1 complex physically associates with minichromosome maintenance proteins 2 (MCM2) to minichromosome maintenance proteins 7 (MCM7) hexamer via TRIM28 and directly regulates the CDC45-MCM-GINS (CMG) helicase retention on chromatin. The regulation of -TRIM28-HSP90B1 on CMG retention is mediated by HSP90B1's chaperoning function. These findings reveal a player that actively regulates replisome retention to prevent fork collapse.

摘要

复制压力是内源性 DNA 损伤的主要来源。尽管已经鉴定出许多在复制叉上的蛋白质来调节叉或复制机制的活性，但非编码 RNA 是否能定位于停滞的叉上并发挥关键的调节作用仍未被探索。在这里，我们鉴定了一个未被表征的长非编码 RNA NONMMUT028956（简称 ），它主要在小鼠胚胎干细胞中表达。在复制叉上积累，以防止叉崩溃和保持基因组稳定性，对小鼠胚胎发生至关重要。从机制上讲，它依赖于共济失调毛细血管扩张症和 Rad3 相关（ATR）信号下游的方式驱动 -TRIM28-HSP90B1 复合物在停滞的叉上组装。-TRIM28-HSP90B1 复合物通过 TRIM28 与微染色体维持蛋白 2（MCM2）物理结合，与微染色体维持蛋白 7（MCM7）六聚体结合，直接调节 CDC45-MCM-GINS（CMG）解旋酶在染色质上的保留。-TRIM28-HSP90B1 对 CMG 保留的调节是由 HSP90B1 的伴侣功能介导的。这些发现揭示了一个积极调节复制体保留以防止叉崩溃的因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/92d064787ac7/sciadv.adf6277-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/c5784d85fe89/sciadv.adf6277-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/81dab5df09c4/sciadv.adf6277-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/e78616335b23/sciadv.adf6277-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/72da29ce085d/sciadv.adf6277-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/78151420c960/sciadv.adf6277-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/50ad287f1947/sciadv.adf6277-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/ee9e52ee98c1/sciadv.adf6277-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/92d064787ac7/sciadv.adf6277-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/c5784d85fe89/sciadv.adf6277-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/81dab5df09c4/sciadv.adf6277-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/e78616335b23/sciadv.adf6277-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/72da29ce085d/sciadv.adf6277-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/78151420c960/sciadv.adf6277-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/50ad287f1947/sciadv.adf6277-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/ee9e52ee98c1/sciadv.adf6277-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7980/9882984/92d064787ac7/sciadv.adf6277-f8.jpg

相似文献

1
-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis.TRIM28-HSP90B1 复合物在复制叉上促进 CMG 解旋酶的保留，以确保干细胞基因组的稳定性和胚胎发生。
Sci Adv. 2023 Jan 27;9(4):eadf6277. doi: 10.1126/sciadv.adf6277.
2
Termination of DNA replication forks: "Breaking up is hard to do".DNA复制叉的终止：“分手很难”
Nucleus. 2015;6(3):187-96. doi: 10.1080/19491034.2015.1035843. Epub 2015 Apr 2.
3
The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.内 S 期检查点直接调控复制延伸，以维持停滞复制叉的完整性。
Proc Natl Acad Sci U S A. 2021 Jun 15;118(24). doi: 10.1073/pnas.2019183118.
4
Cryo-EM Structure of the Fork Protection Complex Bound to CMG at a Replication Fork.与复制叉处的CMG结合的叉保护复合物的冷冻电镜结构
Mol Cell. 2020 Jun 4;78(5):926-940.e13. doi: 10.1016/j.molcel.2020.04.012. Epub 2020 May 4.
5
Essential role of CK2α for the interaction and stability of replication fork factors during DNA synthesis and activation of the S-phase checkpoint.CK2α 在 DNA 合成期间复制叉因子的相互作用和稳定性以及 S 期检验点的激活中起关键作用。
Cell Mol Life Sci. 2022 Jun 4;79(6):339. doi: 10.1007/s00018-022-04374-3.
6
RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks.RAD51- 和 MRE11 依赖性的在解链酶复合体解聚的复制叉处的重新组装。
Nat Struct Mol Biol. 2011 Dec 4;19(1):17-24. doi: 10.1038/nsmb.2177.
7
The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism.真核 CMG 解旋酶在复制叉处：新兴结构揭示了一种出人意料的机制。
Bioessays. 2018 Mar;40(3). doi: 10.1002/bies.201700208. Epub 2018 Feb 6.
8
Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression.Mcm10 具有很强的链退火活性，并限制了转位酶介导的叉回归。
Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):798-803. doi: 10.1073/pnas.1819107116. Epub 2018 Dec 31.
9
Optimizing CMG helicase and CMG-dependent replication assays by designing DNA fork substrates and choosing nucleotide analogues for helicase preloading.通过设计 DNA 分叉底物和选择用于解旋酶预加载的核苷酸类似物来优化 CMG 解旋酶和 CMG 依赖性复制分析。
Methods Enzymol. 2022;672:173-202. doi: 10.1016/bs.mie.2022.02.023. Epub 2022 Mar 25.
10
Tethering of SCF(Dia2) to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase.将SCF（Dia2）与复制体栓系可促进CMG解旋酶的高效泛素化和拆卸。
Curr Biol. 2015 Aug 31;25(17):2254-9. doi: 10.1016/j.cub.2015.07.012. Epub 2015 Aug 6.

引用本文的文献

1
RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells.RetSat 稳定多能干细胞中的有丝分裂染色体分离。
Cell Mol Life Sci. 2024 Aug 22;81(1):366. doi: 10.1007/s00018-024-05413-x.
2
Purification of Long Non-coding RNAs on Replication Forks Using iROND (Isolate RNAs on Nascent DNA).使用iROND（在新生DNA上分离RNA）纯化复制叉上的长链非编码RNA
Bio Protoc. 2023 Nov 5;13(21):e4869. doi: 10.21769/BioProtoc.4869.
3
Characterization of long-term expansion of tree shrew spermatogonial stem cells.树鼩精原干细胞长期扩增的特性研究。

本文引用的文献

1
NORAD-induced Pumilio phase separation is required for genome stability.NORAD 诱导的 Pumilio 相分离是基因组稳定性所必需的。
Nature. 2021 Jul;595(7866):303-308. doi: 10.1038/s41586-021-03633-w. Epub 2021 Jun 9.
2
The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.内 S 期检查点直接调控复制延伸，以维持停滞复制叉的完整性。
Proc Natl Acad Sci U S A. 2021 Jun 15;118(24). doi: 10.1073/pnas.2019183118.
3
The emerging determinants of replication fork stability.新兴的复制叉稳定性决定因素。
Zool Res. 2023 Nov 18;44(6):1080-1094. doi: 10.24272/j.issn.2095-8137.2023.317.
4
DPPA5A suppresses the mutagenic TLS and MMEJ pathways by modulating the cryptic splicing of and in mouse embryonic stem cells.DPPA5A 通过调节 和 在小鼠胚胎干细胞中的剪接来抑制诱变的 TLS 和 MMEJ 途径。
Proc Natl Acad Sci U S A. 2023 Jul 25;120(30):e2305187120. doi: 10.1073/pnas.2305187120. Epub 2023 Jul 17.
Nucleic Acids Res. 2021 Jul 21;49(13):7224-7238. doi: 10.1093/nar/gkab344.
4
Ubiquitylation at Stressed Replication Forks: Mechanisms and Functions.复制叉压力下的泛素化：机制与功能。
Trends Cell Biol. 2021 Jul;31(7):584-597. doi: 10.1016/j.tcb.2021.01.008. Epub 2021 Feb 18.
5
ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility.ARMC12 调控精子发生过程中的时空线粒体动态，是雄性生育力所必需的。
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6). doi: 10.1073/pnas.2018355118.
6
Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells.Dcaf11 激活 Zscan4 介导的早期胚胎和胚胎干细胞中的替代性端粒延长。
Cell Stem Cell. 2021 Apr 1;28(4):732-747.e9. doi: 10.1016/j.stem.2020.11.018. Epub 2020 Dec 23.
7
Gene regulation by long non-coding RNAs and its biological functions.长非编码 RNA 的基因调控及其生物学功能。
Nat Rev Mol Cell Biol. 2021 Feb;22(2):96-118. doi: 10.1038/s41580-020-00315-9. Epub 2020 Dec 22.
8
TRF2-mediated telomere protection is dispensable in pluripotent stem cells.TRF2 介导的端粒保护在多能干细胞中是可有可无的。
Nature. 2021 Jan;589(7840):110-115. doi: 10.1038/s41586-020-2959-4. Epub 2020 Nov 25.
9
TRF2-independent chromosome end protection during pluripotency.多能性期间 TRF2 非依赖性染色体末端保护。
Nature. 2021 Jan;589(7840):103-109. doi: 10.1038/s41586-020-2960-y. Epub 2020 Nov 25.
10
Spotlight on the Replisome: Aetiology of DNA Replication-Associated Genetic Diseases.聚焦复制体：与 DNA 复制相关的遗传疾病的病因。
Trends Genet. 2021 Apr;37(4):317-336. doi: 10.1016/j.tig.2020.09.008. Epub 2020 Oct 8.