• 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

哺乳动物 Swi5-Sfr1 复合物在同源重组中通过 DNA 链断裂修复的作用。

Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination.

机构信息

Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

出版信息

PLoS Genet. 2010 Oct 14;6(10):e1001160. doi: 10.1371/journal.pgen.1001160.

DOI:10.1371/journal.pgen.1001160
PMID:20976249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2954829/
Abstract

In fission yeast, the Swi5-Sfr1 complex plays an important role in homologous recombination (HR), a pathway crucial for the maintenance of genomic integrity. Here we identify and characterize mammalian Swi5 and Sfr1 homologues. Mouse Swi5 and Sfr1 are nuclear proteins that form a complex in vivo and in vitro. Swi5 interacts in vitro with Rad51, the DNA strand-exchange protein which functions during HR. By generating Swi5(-/-) and Sfr1(-/-) embryonic stem cell lines, we found that both proteins are mutually interdependent for their stability. Importantly, the Swi5-Sfr1 complex plays a role in HR when Rad51 function is perturbed in vivo by expression of a BRC peptide from BRCA2. Swi5(-/-) and Sfr1(-/-) cells are selectively sensitive to agents that cause DNA strand breaks, in particular ionizing radiation, camptothecin, and the Parp inhibitor olaparib. Consistent with a role in HR, sister chromatid exchange induced by Parp inhibition is attenuated in Swi5(-/-) and Sfr1(-/-) cells, and chromosome aberrations are increased. Thus, Swi5-Sfr1 is a newly identified complex required for genomic integrity in mammalian cells with a specific role in the repair of DNA strand breaks.

摘要

在裂殖酵母中，Swi5-Sfr1 复合物在同源重组（HR）中发挥重要作用，HR 是维持基因组完整性的关键途径。在这里，我们鉴定并描述了哺乳动物 Swi5 和 Sfr1 同源物。小鼠 Swi5 和 Sfr1 是核蛋白，可在体内和体外形成复合物。Swi5 在体外与 Rad51 相互作用，Rad51 是在 HR 期间起作用的 DNA 链交换蛋白。通过生成 Swi5(-/-)和 Sfr1(-/-)胚胎干细胞系，我们发现这两种蛋白质在其稳定性上相互依赖。重要的是，当 BRCA2 的 BRC 肽表达体内扰乱 Rad51 功能时，Swi5-Sfr1 复合物在 HR 中发挥作用。Swi5(-/-)和 Sfr1(-/-)细胞对引起 DNA 链断裂的试剂（特别是电离辐射、喜树碱和 Parp 抑制剂奥拉帕利）具有选择性敏感性。与 HR 作用一致，Swi5(-/-)和 Sfr1(-/-)细胞中 Parp 抑制诱导的姐妹染色单体交换减弱，染色体畸变增加。因此，Swi5-Sfr1 是哺乳动物细胞中鉴定出的一种新的必需复合物，对于基因组完整性具有特定作用，特别是在修复 DNA 链断裂方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/c3f1877b938f/pgen.1001160.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/6ad6636303cd/pgen.1001160.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/6d34d1f84ccd/pgen.1001160.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/ca3c83ac0994/pgen.1001160.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/5c5bad64cbcc/pgen.1001160.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/c3f1877b938f/pgen.1001160.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/6ad6636303cd/pgen.1001160.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/6d34d1f84ccd/pgen.1001160.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/ca3c83ac0994/pgen.1001160.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/5c5bad64cbcc/pgen.1001160.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d8/2954829/c3f1877b938f/pgen.1001160.g005.jpg

相似文献

1
Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination.哺乳动物 Swi5-Sfr1 复合物在同源重组中通过 DNA 链断裂修复的作用。
PLoS Genet. 2010 Oct 14;6(10):e1001160. doi: 10.1371/journal.pgen.1001160.
2
Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex.合作相互作用促进了 Swi5-Sfr1 辅助因子复合物对 Rad51 的刺激。
Elife. 2020 Mar 24;9:e52566. doi: 10.7554/eLife.52566.
3
Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination.RAD51-SWI5-SFR1复合体在同源重组中的作用。
Nucleic Acids Res. 2016 Jul 27;44(13):6242-51. doi: 10.1093/nar/gkw375. Epub 2016 Apr 30.
4
Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex.鼠 Swi5-Sfr1 异源二聚体复合物的 Rad51 预联丝稳定功能。
Nucleic Acids Res. 2012 Aug;40(14):6558-69. doi: 10.1093/nar/gks305. Epub 2012 Apr 9.
5
Fission yeast Swi5-Sfr1 protein complex, an activator of Rad51 recombinase, forms an extremely elongated dogleg-shaped structure.裂殖酵母 Swi5-Sfr1 蛋白复合物是 Rad51 重组酶的激活因子，形成极其细长的狗腿形结构。
J Biol Chem. 2011 Dec 16;286(50):43569-76. doi: 10.1074/jbc.M111.303339. Epub 2011 Oct 27.
6
Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5-Sfr1.通过 Rad51 辅助因子 Swi5-Sfr1 对 DNA 修复进行磷酸化调控。
J Biol Chem. 2023 Aug;299(8):104929. doi: 10.1016/j.jbc.2023.104929. Epub 2023 Jun 16.
7
Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex.SWI5-SFR1 复合物增强 RAD51 预丝体的 ADP 释放。
Nucleic Acids Res. 2014 Jan;42(1):349-58. doi: 10.1093/nar/gkt879. Epub 2013 Sep 27.
8
Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes.裂殖酵母Swi5/Sfr1和Rhp55/Rhp57对Rhp51依赖性重组结果具有不同的调控作用。
EMBO J. 2007 Mar 7;26(5):1352-62. doi: 10.1038/sj.emboj.7601582. Epub 2007 Feb 15.
9
The role of the human SWI5-MEI5 complex in homologous recombination repair.人 SWI5-MEI5 复合物在同源重组修复中的作用。
J Biol Chem. 2011 Mar 18;286(11):9888-93. doi: 10.1074/jbc.M110.207290. Epub 2011 Jan 20.
10
Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.Swi5-Sfr1 蛋白通过在预链交换丝中组织 DNA 碱基来刺激 Rad51 介导的 DNA 链交换反应。
Nucleic Acids Res. 2014 Feb;42(4):2358-65. doi: 10.1093/nar/gkt1257. Epub 2013 Dec 3.

引用本文的文献

1
Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum.通过负鼠第一波精子发生的转录组学鉴定胎盘哺乳动物生殖系生物学中的进化创新。
Dev Cell. 2025 Feb 24;60(4):646-664.e8. doi: 10.1016/j.devcel.2024.10.013. Epub 2024 Nov 12.
2
CDK phosphorylation of Sfr1 downregulates Rad51 function in late-meiotic homolog invasions.CDK 磷酸化 Sfr1 下调 Rad51 功能，以阻止减数分裂后期同源物入侵。
EMBO J. 2024 Oct;43(19):4356-4383. doi: 10.1038/s44318-024-00205-2. Epub 2024 Aug 22.
3
Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly using distinct mechanisms.

本文引用的文献

1
Crossover invariance determined by partner choice for meiotic DNA break repair.由配偶选择决定的减数分裂 DNA 断裂修复的交叉不变性。
Cell. 2010 Jul 23;142(2):243-55. doi: 10.1016/j.cell.2010.05.041.
2
PARP inhibition: PARP1 and beyond.聚腺苷二磷酸核糖聚合酶抑制剂：PARP1 及其他。
Nat Rev Cancer. 2010 Apr;10(4):293-301. doi: 10.1038/nrc2812. Epub 2010 Mar 4.
3
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.非同源 DNA 末端连接途径修复双链 DNA 断裂的机制。
Hop2-Mnd1 和 Swi5-Sfr1 通过不同的机制促进 Dmc1 丝组装。
Nucleic Acids Res. 2023 Sep 8;51(16):8550-8562. doi: 10.1093/nar/gkad561.
4
The Hop2-Mnd1 Complex and Its Regulation of Homologous Recombination.Hop2-Mnd1 复合物及其对同源重组的调控。
Biomolecules. 2023 Apr 10;13(4):662. doi: 10.3390/biom13040662.
5
Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer.三阴性乳腺癌中转录因子 E4F1 对 ATM/ATR-CHK1 轴的多级调控
Int J Mol Sci. 2022 Aug 16;23(16):9217. doi: 10.3390/ijms23169217.
6
Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex.由 SWS1-SWSAP1-SPIDR 复合物控制的同源重组的不同途径。
Nat Commun. 2021 Jul 12;12(1):4255. doi: 10.1038/s41467-021-24205-6.
7
Mapping and Analysis of Swi5 and Sfr1 Phosphorylation Sites.Swi5 和 Sfr1 磷酸化位点的作图与分析。
Genes (Basel). 2021 Jun 30;12(7):1014. doi: 10.3390/genes12071014.
8
Two auxiliary factors promote Dmc1-driven DNA strand exchange via stepwise mechanisms.两个辅助因子通过逐步机制促进 Dmc1 驱动的 DNA 链交换。
Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12062-12070. doi: 10.1073/pnas.1917419117. Epub 2020 May 15.
9
Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex.合作相互作用促进了 Swi5-Sfr1 辅助因子复合物对 Rad51 的刺激。
Elife. 2020 Mar 24;9:e52566. doi: 10.7554/eLife.52566.
10
A mutant form of Dmc1 that bypasses the requirement for accessory protein Mei5-Sae3 reveals independent activities of Mei5-Sae3 and Rad51 in Dmc1 filament stability.一种突变形式的 Dmc1 可以绕过辅助蛋白 Mei5-Sae3 的需求，揭示了 Mei5-Sae3 和 Rad51 在 Dmc1 丝稳定性中的独立活性。
PLoS Genet. 2019 Dec 2;15(12):e1008217. doi: 10.1371/journal.pgen.1008217. eCollection 2019 Dec.
Annu Rev Biochem. 2010;79:181-211. doi: 10.1146/annurev.biochem.052308.093131.
4
Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis.有丝分裂同源重组维持基因组稳定性并抑制肿瘤发生。
Nat Rev Mol Cell Biol. 2010 Mar;11(3):196-207. doi: 10.1038/nrm2851.
5
The fission yeast Rad32(Mre11)-Rad50-Nbs1 complex acts both upstream and downstream of checkpoint signaling in the S-phase DNA damage checkpoint.裂殖酵母 Rad32（Mre11）-Rad50-Nbs1 复合物在 S 期 DNA 损伤检查点的检查点信号中既在上游又在下游发挥作用。
Genetics. 2010 Apr;184(4):887-97. doi: 10.1534/genetics.109.113019. Epub 2010 Jan 11.
6
Nucleases and helicases take center stage in homologous recombination.核酸酶和解旋酶在同源重组中起核心作用。
Trends Biochem Sci. 2009 May;34(5):264-72. doi: 10.1016/j.tibs.2009.01.010. Epub 2009 Apr 15.
7
The BRC repeats of BRCA2 modulate the DNA-binding selectivity of RAD51.BRCA2的BRC重复序列调节RAD51的DNA结合选择性。
Cell. 2009 Mar 20;136(6):1032-43. doi: 10.1016/j.cell.2009.02.019.
8
The Mei5-Sae3 protein complex mediates Dmc1 activity in Saccharomyces cerevisiae.Mei5-Sae3蛋白复合物介导酿酒酵母中的Dmc1活性。
J Biol Chem. 2009 May 1;284(18):11766-70. doi: 10.1074/jbc.C900023200. Epub 2009 Mar 7.
9
Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint.Mus81、Rhp51（Rad51）和Rqh1形成了S期DNA损伤检查点所需的上位性途径。
Mol Biol Cell. 2009 Feb;20(3):819-33. doi: 10.1091/mbc.e08-08-0798. Epub 2008 Nov 26.
10
Genetic analysis reveals different roles of Schizosaccharomyces pombe sfr1/dds20 in meiotic and mitotic DNA recombination and repair.遗传分析揭示了粟酒裂殖酵母sfr1/dds20在减数分裂和有丝分裂DNA重组及修复中的不同作用。
Curr Genet. 2008 Oct;54(4):197-211. doi: 10.1007/s00294-008-0212-z. Epub 2008 Sep 4.