• 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

结构洞察 BCDX2 复合物在同源重组中的功能。

Structural insights into BCDX2 complex function in homologous recombination.

机构信息

Department of Biochemistry & Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.

出版信息

Nature. 2023 Jul;619(7970):640-649. doi: 10.1038/s41586-023-06219-w. Epub 2023 Jun 21.

DOI:10.1038/s41586-023-06219-w
PMID:37344589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10712684/
Abstract

Homologous recombination (HR) fulfils a pivotal role in the repair of DNA double-strand breaks and collapsed replication forks. HR depends on the products of several paralogues of RAD51, including the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 (BCDX2). BCDX2 functions as a mediator of nucleoprotein filament assembly by RAD51 and single-stranded DNA (ssDNA) during HR, but its mechanism remains undefined. Here we report cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis yields insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Moreover, our cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer inactivate DNA binding and the HR mediator activity of BCDX2. Our findings shed light on the role of BCDX2 in HR and provide a foundation for understanding how pathogenic alterations in BCDX2 impact genome repair.

摘要

同源重组（HR）在修复 DNA 双链断裂和崩溃的复制叉中起着关键作用。HR 依赖于 RAD51 的几个同源物的产物，包括 RAD51B、RAD51C、RAD51D 和 XRCC2（BCDX2）的四聚体复合物。BCDX2 在 HR 期间作为 RAD51 和单链 DNA（ssDNA）介导核蛋白丝组装的介质，但其机制尚不清楚。在这里，我们报告了apo 和 ssDNA 结合状态下人类 BCDX2 的低温电子显微镜重建。这些结构揭示了 RAD51B、RAD51C 和 RAD51D 的氨基末端结构域如何参与支撑复合物形成和 ssDNA 结合特异性的亚基间相互作用。单分子 DNA 幕分析深入了解了 BCDX2 如何增强 RAD51-ssDNA 核蛋白丝组装。此外，我们的低温电子显微镜和功能分析解释了在癌症患者中发现的 RAD51C 改变如何使 BCDX2 的 DNA 结合和 HR 介质活性失活。我们的研究结果阐明了 BCDX2 在 HR 中的作用，并为理解 BCDX2 中的致病改变如何影响基因组修复提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/510846646e2c/nihms-1947754-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/6c878919f2cf/nihms-1947754-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/b63ae4c1d216/nihms-1947754-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/41d33d298e21/nihms-1947754-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/9bc616f59378/nihms-1947754-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/defeb745fe58/nihms-1947754-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/ccc037861b32/nihms-1947754-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/c06082eee054/nihms-1947754-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/d17b7a8c91f2/nihms-1947754-f0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/7f0cacf3689f/nihms-1947754-f0016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/c94840c5dccc/nihms-1947754-f0017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/f8e4b5794869/nihms-1947754-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/2745edf69fef/nihms-1947754-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/dd5990dec872/nihms-1947754-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/d4c1ac9bf2f5/nihms-1947754-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/b6efb853bc08/nihms-1947754-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/df7ad6df6bb4/nihms-1947754-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/510846646e2c/nihms-1947754-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/6c878919f2cf/nihms-1947754-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/b63ae4c1d216/nihms-1947754-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/41d33d298e21/nihms-1947754-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/9bc616f59378/nihms-1947754-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/defeb745fe58/nihms-1947754-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/ccc037861b32/nihms-1947754-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/c06082eee054/nihms-1947754-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/d17b7a8c91f2/nihms-1947754-f0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/7f0cacf3689f/nihms-1947754-f0016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/c94840c5dccc/nihms-1947754-f0017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/f8e4b5794869/nihms-1947754-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/2745edf69fef/nihms-1947754-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/dd5990dec872/nihms-1947754-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/d4c1ac9bf2f5/nihms-1947754-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/b6efb853bc08/nihms-1947754-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/df7ad6df6bb4/nihms-1947754-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/218d/10712684/510846646e2c/nihms-1947754-f0007.jpg

相似文献

1
Structural insights into BCDX2 complex function in homologous recombination.结构洞察 BCDX2 复合物在同源重组中的功能。
Nature. 2023 Jul;619(7970):640-649. doi: 10.1038/s41586-023-06219-w. Epub 2023 Jun 21.
2
Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor.RAD51B-RAD51C-RAD51D-XRCC2 肿瘤抑制因子的结构与功能。
Nature. 2023 Jul;619(7970):650-657. doi: 10.1038/s41586-023-06179-1. Epub 2023 Jun 21.
3
Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA.BCDX2 介导 RAD51 在短 ssDNA 链段和叉形 DNA 上引发的机制。
Nucleic Acids Res. 2024 Oct 28;52(19):11738-11752. doi: 10.1093/nar/gkae770.
4
Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway.Rad51 旁系同源复合物 BCDX2 和 CX3 在 BRCA1-BRCA2 依赖性同源重组途径的不同阶段发挥作用。
Mol Cell Biol. 2013 Jan;33(2):387-95. doi: 10.1128/MCB.00465-12. Epub 2012 Nov 12.
5
Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and replication forks as visualized by electron microscopy.电子显微镜观察到，环形 Rad51 旁系蛋白复合物与 Holliday 连接点和复制叉结合。
J Biol Chem. 2010 Apr 30;285(18):13349-56. doi: 10.1074/jbc.M109.074286. Epub 2010 Mar 5.
6
Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination.Rad51 和 Dmc1 在同源重组中独特的错配容忍机制。
Nucleic Acids Res. 2021 Dec 16;49(22):13135-13149. doi: 10.1093/nar/gkab1141.
7
Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex.人源Rad51B、Rad51C、Rad51D和Xrcc2蛋白复合体与分支DNA链的优先结合及链退火活性
Nucleic Acids Res. 2004 May 11;32(8):2556-65. doi: 10.1093/nar/gkh578. Print 2004.
8
High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy.通过电子冷冻显微镜解析单链DNA上突触前RAD51细丝的高分辨率结构。
Nucleic Acids Res. 2016 Nov 2;44(19):9017-9030. doi: 10.1093/nar/gkw783. Epub 2016 Sep 5.
9
Dissecting the Recombination Mediator Activity of BRCA2 Using Biochemical Methods.运用生化方法剖析BRCA2的重组介导活性
Methods Enzymol. 2018;600:479-511. doi: 10.1016/bs.mie.2017.11.018.
10
Determining the RAD51-DNA Nucleoprotein Filament Structure and Function by Cryo-Electron Microscopy.通过冷冻电子显微镜确定RAD51-DNA核蛋白丝的结构与功能
Methods Enzymol. 2018;600:179-199. doi: 10.1016/bs.mie.2017.12.002. Epub 2018 Feb 1.

引用本文的文献

1
Structural mechanism of strand exchange by the RAD51 filament.RAD51细丝进行链交换的结构机制。
Elife. 2025 Aug 18;14:RP107114. doi: 10.7554/eLife.107114.
2
Mechanism of Rad51 filament formation by Rad52 and Rad55-Rad57 in homologous recombination.Rad52和Rad55-Rad57在同源重组中形成Rad51细丝的机制。
Nat Commun. 2025 Jul 21;16(1):6685. doi: 10.1038/s41467-025-61811-0.
3
Comprehensive RAD51C ovarian cancer variant analysis uncouples homologous recombination and replicative functions.RAD51C在卵巢癌中的全面变异分析揭示了同源重组与复制功能的解偶联。

本文引用的文献

1
Homologous recombination-deficient mutation cluster in tumor suppressor identified by comprehensive analysis of cancer variants.通过对癌症变异的综合分析鉴定出肿瘤抑制因子中同源重组缺陷突变簇。
Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2202727119. doi: 10.1073/pnas.2202727119. Epub 2022 Sep 13.
2
DNA repair as a shared hallmark in cancer and ageing.DNA 修复作为癌症和衰老的共同特征。
Mol Oncol. 2022 Sep;16(18):3352-3379. doi: 10.1002/1878-0261.13285. Epub 2022 Jul 28.
3
Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination.
Nat Commun. 2025 Jul 16;16(1):6539. doi: 10.1038/s41467-025-61283-2.
4
A large C-terminal Rad52 segment acts as a chaperone to Form and Stabilize Rad51 Filaments.一个大的C端Rad52片段作为伴侣蛋白来形成并稳定Rad51丝。
Nat Commun. 2025 Jul 1;16(1):5589. doi: 10.1038/s41467-025-60664-x.
5
Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin.FIGNL1在使RAD51与DNA和染色质解离中的分子基础。
Science. 2025 Jan 24;387(6732):426-431. doi: 10.1126/science.adr7920. Epub 2024 Dec 5.
6
Systematic identification of pathogenic variants of non-small cell lung cancer in the promoters of DNA-damage repair genes.DNA损伤修复基因启动子中非小细胞肺癌致病变异的系统鉴定
EBioMedicine. 2024 Dec;110:105480. doi: 10.1016/j.ebiom.2024.105480. Epub 2024 Dec 3.
7
Using AI-predicted protein structures as a reference to predict loss-of-function activity in tumor suppressor breast cancer genes.以人工智能预测的蛋白质结构为参考来预测乳腺癌抑癌基因的功能丧失活性。
Comput Struct Biotechnol J. 2024 Oct 5;23:3472-3480. doi: 10.1016/j.csbj.2024.10.008. eCollection 2024 Dec.
8
FIGL1 attenuates meiotic interhomolog repair and is counteracted by the RAD51 paralog XRCC2 and the chromosome axis protein ASY1 during meiosis.FIGL1 可减弱减数分裂同源重组修复，在减数分裂过程中被 RAD51 旁系同源物 XRCC2 和染色体轴蛋白 ASY1 拮抗。
New Phytol. 2024 Dec;244(6):2442-2457. doi: 10.1111/nph.20181. Epub 2024 Oct 17.
9
The role of RAD51 regulators and variants in primary ovarian insufficiency, endometriosis, and polycystic ovary syndrome.RAD51调控因子及变异体在原发性卵巢功能不全、子宫内膜异位症和多囊卵巢综合征中的作用
NAR Mol Med. 2024 Sep 28;1(4):ugae010. doi: 10.1093/narmme/ugae010. eCollection 2024 Oct.
10
High-resolution functional mapping of RAD51C by saturation genome editing.RAD51C 的高分辨率功能图谱通过饱和基因组编辑。
Cell. 2024 Oct 3;187(20):5719-5734.e19. doi: 10.1016/j.cell.2024.08.039. Epub 2024 Sep 18.
Rad51 和 Dmc1 在同源重组中独特的错配容忍机制。
Nucleic Acids Res. 2021 Dec 16;49(22):13135-13149. doi: 10.1093/nar/gkab1141.
4
Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function.线虫 RAD51 同源物的核苷酸校正功能有助于 RAD51 丝最佳功能的发挥。
Nat Commun. 2021 Sep 20;12(1):5545. doi: 10.1038/s41467-021-25830-x.
5
Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
6
Single-Stranded DNA Curtains for Single-Molecule Visualization of Rad51-ssDNA Filament Dynamics.单链 DNA 幕布用于单分子可视化 Rad51-ssDNA 丝束动力学。
Methods Mol Biol. 2021;2281:193-207. doi: 10.1007/978-1-0716-1290-3_11.
7
The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination.Rad51 同源物复合物 Rad55-Rad57 在同源重组过程中充当分子伴侣。
Mol Cell. 2021 Mar 4;81(5):1043-1057.e8. doi: 10.1016/j.molcel.2020.12.019. Epub 2021 Jan 8.
8
Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins.单分子分析揭示了中介蛋白对 Rad51 丝核酶形成和延伸的协同刺激作用。
Mol Cell. 2021 Mar 4;81(5):1058-1073.e7. doi: 10.1016/j.molcel.2020.12.020. Epub 2021 Jan 8.
9
Mechanism of strand exchange from RecA-DNA synaptic and D-loop structures.RecA-DNA 突触和 D 环结构中链交换的机制。
Nature. 2020 Oct;586(7831):801-806. doi: 10.1038/s41586-020-2820-9. Epub 2020 Oct 14.
10
UCSF ChimeraX: Structure visualization for researchers, educators, and developers.UCSF ChimeraX：面向研究人员、教育工作者和开发者的结构可视化工具。
Protein Sci. 2021 Jan;30(1):70-82. doi: 10.1002/pro.3943. Epub 2020 Oct 22.