Rad51缺陷的脊椎动物细胞在细胞死亡前会积累染色体断裂。
Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death.
作者信息
Sonoda E, Sasaki M S, Buerstedde J M, Bezzubova O, Shinohara A, Ogawa H, Takata M, Yamaguchi-Iwai Y, Takeda S
机构信息
Bayer Chair, Department of Molecular Immunology and Allergology, Faculty of Medicine, Kyoto University, Japan.
出版信息
EMBO J. 1998 Jan 15;17(2):598-608. doi: 10.1093/emboj/17.2.598.
Abstract
Yeast rad51 mutants are viable, but extremely sensitive to gamma-rays due to defective repair of double-strand breaks. In contrast, disruption of the murine RAD51 homologue is lethal, indicating an essential role of Rad51 in vertebrate cells. We generated clones of the chicken B lymphocyte line DT40 carrying a human RAD51 transgene under the control of a repressible promoter and subsequently disrupted the endogenous RAD51 loci. Upon inhibition of the RAD51 transgene, Rad51- cells accumulated in the G2/M phase of the cell cycle before dying. Chromosome analysis revealed that most metaphase-arrested Rad51- cells carried isochromatid-type breaks. In conclusion, Rad51 fulfils an essential role in the repair of spontaneously occurring chromosome breaks in proliferating cells of higher eukaryotes.
摘要
酵母rad51突变体是可存活的，但由于双链断裂修复缺陷而对γ射线极其敏感。相比之下，小鼠RAD51同源物的破坏是致死性的，这表明Rad51在脊椎动物细胞中起重要作用。我们构建了鸡B淋巴细胞系DT40的克隆，其携带在可抑制启动子控制下的人RAD51转基因，随后破坏内源性RAD51基因座。在抑制RAD51转基因后，Rad51缺陷细胞在死亡前在细胞周期的G2/M期积累。染色体分析显示，大多数中期停滞的Rad51缺陷细胞携带等染色单体型断裂。总之，Rad51在高等真核生物增殖细胞中自发发生的染色体断裂修复中起重要作用。
相似文献
1
Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death.Rad51缺陷的脊椎动物细胞在细胞死亡前会积累染色体断裂。
EMBO J. 1998 Jan 15;17(2):598-608. doi: 10.1093/emboj/17.2.598.
2
Collaborative roles of gammaH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair.γH2AX与Rad51旁系同源物Xrcc3在同源重组修复中的协同作用。
DNA Repair (Amst). 2007 Mar 1;6(3):280-92. doi: 10.1016/j.dnarep.2006.10.025. Epub 2006 Nov 22.
3
Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.Mre11对于脊椎动物细胞中染色体DNA的维持至关重要。
EMBO J. 1999 Dec 1;18(23):6619-29. doi: 10.1093/emboj/18.23.6619.
4
Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs.五个Rad51旁系同源物基因敲除突变体中的染色体不稳定性及有缺陷的重组修复
Mol Cell Biol. 2001 Apr;21(8):2858-66. doi: 10.1128/MCB.21.8.2858-2866.2001.
5
Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells.Rad52在维持脊椎动物细胞染色体完整性方面部分替代了Rad51旁系同源物XRCC3。
EMBO J. 2001 Oct 1;20(19):5513-20. doi: 10.1093/emboj/20.19.5513.
6
The mammalian mismatch repair protein MSH2 is required for correct MRE11 and RAD51 relocalization and for efficient cell cycle arrest induced by ionizing radiation in G2 phase.哺乳动物错配修复蛋白MSH2是正确的MRE11和RAD51重新定位以及电离辐射诱导的G2期有效细胞周期停滞所必需的。
Oncogene. 2003 Apr 10;22(14):2110-20. doi: 10.1038/sj.onc.1206254.
7
Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination.哺乳动物的XRCC2通过同源重组促进DNA双链断裂的修复。
Nature. 1999 Sep 23;401(6751):397-9. doi: 10.1038/43932.
8
XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells.在G1期的XRCC4在G1期检查点缺陷细胞中抑制S/G2期的同源重组。
Oncogene. 2007 Apr 26;26(19):2769-80. doi: 10.1038/sj.onc.1210075. Epub 2006 Oct 23.
9
Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51.Xrcc3在早期被招募到DNA双链断裂处，且与Rad51无关。
J Cell Biochem. 2004 Oct 15;93(3):429-36. doi: 10.1002/jcb.20232.
10
Synergistic actions of Rad51 and Rad52 in recombination and DNA repair.Rad51与Rad52在重组和DNA修复中的协同作用。
Nature. 1998 Jan 22;391(6665):401-4. doi: 10.1038/34937.
引用本文的文献
1
The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.同源重组因子BRCA2和PALB2与错配修复途径相互作用，以维持着丝粒稳定性和细胞活力。
Cell Rep. 2025 Feb 25;44(2):115259. doi: 10.1016/j.celrep.2025.115259. Epub 2025 Jan 31.
2
The Possible Crystallization Process in the Origin of Bacteria, Archaea, Viruses, and Mobile Elements.细菌、古菌、病毒和移动元件起源中可能的结晶过程。
Biology (Basel). 2024 Dec 24;14(1):3. doi: 10.3390/biology14010003.
3
Heavy water inhibits DNA double-strand break repairs and disturbs cellular transcription, presumably via quantum-level mechanisms of kinetic isotope effects on hydrolytic enzyme reactions.重水会抑制 DNA 双链断裂修复，并扰乱细胞转录，这可能是通过水解酶反应的动力学同位素效应的量子水平机制。
PLoS One. 2024 Oct 3;19(10):e0309689. doi: 10.1371/journal.pone.0309689. eCollection 2024.
4
BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode.BRCA2 通过保守的相互作用模式稳定 RAD51 和 DMC1 核蛋白丝。
Nat Commun. 2024 Sep 27;15(1):8292. doi: 10.1038/s41467-024-52699-3.
5
The multifaceted roles of the Ctf4 replisome hub in the maintenance of genome integrity.Ctf4 复制体枢纽在维持基因组完整性方面的多方面作用。
DNA Repair (Amst). 2024 Oct;142:103742. doi: 10.1016/j.dnarep.2024.103742. Epub 2024 Aug 12.
6
Characterization and regulation of cell cycle-independent noncanonical gene targeting.细胞周期非依赖性非规范基因靶向的特征与调控。
Nat Commun. 2024 Jun 18;15(1):5044. doi: 10.1038/s41467-024-49385-9.
7
RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.RNF4 通过促进 DNA 复制来维持 Myc 驱动的肿瘤发生。
J Clin Invest. 2024 Mar 26;134(10):e167419. doi: 10.1172/JCI167419.
8
Cryo-EM structures of RAD51 assembled on nucleosomes containing a DSB site.RAD51 组装在含有 DSB 位点的核小体上的冷冻电镜结构。
Nature. 2024 Apr;628(8006):212-220. doi: 10.1038/s41586-024-07196-4. Epub 2024 Mar 20.
9
Analysis of the indispensable RAD51 cofactor BRCA2 in , a Basidiomycota yeast.分析担子菌酵母 中不可或缺的 RAD51 辅助因子 BRCA2。
Life Sci Alliance. 2023 Nov 28;7(2). doi: 10.26508/lsa.202302342. Print 2024 Feb.
10
FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination.FIGNL1 AAA+ ATPase 在减数前 DNA 复制和减数重组中重塑 RAD51 和 DMC1 丝。
Nat Commun. 2023 Oct 27;14(1):6857. doi: 10.1038/s41467-023-42576-w.
本文引用的文献
1
Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism.霍利迪连接体通过一种不依赖于RecA同源物的机制在复制突变体中积累。
Cell. 1997 Jul 11;90(1):87-96. doi: 10.1016/s0092-8674(00)80316-5.
2
RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein.RAB22和RAB163/小鼠BRCA2：与RAD51蛋白特异性相互作用的蛋白质。
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6927-32. doi: 10.1073/pnas.94.13.6927.
3
Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2.缺乏Brca2的小鼠中由Rad51介导的胚胎致死性和辐射超敏反应。
Nature. 1997 Apr 24;386(6627):804-10. doi: 10.1038/386804a0.
4
Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination.破坏小鼠RAD54会降低电离辐射抗性和同源重组。
Cell. 1997 Apr 18;89(2):195-204. doi: 10.1016/s0092-8674(00)80199-3.
5
Reduced X-ray resistance and homologous recombination frequencies in a RAD54-/- mutant of the chicken DT40 cell line.鸡DT40细胞系RAD54基因敲除突变体中X射线抗性和同源重组频率降低。
Cell. 1997 Apr 18;89(2):185-93. doi: 10.1016/s0092-8674(00)80198-1.
6
A super new twist on the initiation of meiotic recombination.减数分裂重组起始的一个全新转折。
Cell. 1997 Apr 18;89(2):163-6. doi: 10.1016/s0092-8674(00)80194-4.
7
Is RecF a DNA replication protein?RecF 是一种 DNA 复制蛋白吗？
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3483-4. doi: 10.1073/pnas.94.8.3483.
8
Apoptosis by death factor.死亡因子介导的细胞凋亡
Cell. 1997 Feb 7;88(3):355-65. doi: 10.1016/s0092-8674(00)81874-7.
9
An approximately half set of histone genes is enough for cell proliferation and a lack of several histone variants causes protein pattern changes in the DT40 chicken B cell line.大约半套组蛋白基因就足以支持细胞增殖，并且缺乏几种组蛋白变体可导致DT40鸡B细胞系中的蛋白质模式发生变化。
J Mol Biol. 1997 Jan 31;265(4):394-408. doi: 10.1006/jmbi.1996.0733.
10
Association of BRCA1 with Rad51 in mitotic and meiotic cells.有丝分裂和减数分裂细胞中BRCA1与Rad51的关联。
Cell. 1997 Jan 24;88(2):265-75. doi: 10.1016/s0092-8674(00)81847-4.
Zotero 插件