细胞如何确保正确修复 DNA 双链断裂。
How cells ensure correct repair of DNA double-strand breaks.
机构信息
From the Department of Molecular Biology and Biochemistry, Rutgers, State University of New Jersey, Piscataway, New Jersey 08540.
From the Department of Molecular Biology and Biochemistry, Rutgers, State University of New Jersey, Piscataway, New Jersey 08540
出版信息
J Biol Chem. 2018 Jul 6;293(27):10502-10511. doi: 10.1074/jbc.TM118.000371. Epub 2018 Feb 5.
Abstract
DNA double-strand breaks (DSBs) arise regularly in cells and when left unrepaired cause senescence or cell death. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are the two major DNA-repair pathways. Whereas HR allows faithful DSB repair and healthy cell growth, NHEJ has higher potential to contribute to mutations and malignancy. Many regulatory mechanisms influence which of these two pathways is used in DSB repair. These mechanisms depend on the cell cycle, post-translational modifications, and chromatin effects. Here, we summarize current research into these mechanisms, with a focus on mammalian cells, and also discuss repair by "alternative end-joining" and single-strand annealing.
摘要
DNA 双链断裂 (DSBs) 在细胞中经常出现，如果不修复，会导致衰老或细胞死亡。同源重组 (HR) 和非同源末端连接 (NHEJ) 是两种主要的 DNA 修复途径。虽然 HR 允许忠实的 DSB 修复和健康的细胞生长，但 NHEJ 更有可能导致突变和恶性肿瘤。许多调节机制影响两种途径中哪一种用于 DSB 修复。这些机制取决于细胞周期、翻译后修饰和染色质效应。在这里，我们总结了目前对这些机制的研究，重点是哺乳动物细胞，还讨论了“替代性末端连接”和单链退火的修复。
相似文献
1
How cells ensure correct repair of DNA double-strand breaks.细胞如何确保正确修复 DNA 双链断裂。
J Biol Chem. 2018 Jul 6;293(27):10502-10511. doi: 10.1074/jbc.TM118.000371. Epub 2018 Feb 5.
2
The role of nonhomologous DNA end joining, conservative homologous recombination, and single-strand annealing in the cell cycle-dependent repair of DNA double-strand breaks induced by H(2)O(2) in mammalian cells.非同源DNA末端连接、保守同源重组和单链退火在哺乳动物细胞中由H₂O₂诱导的DNA双链断裂的细胞周期依赖性修复中的作用。
Radiat Res. 2008 Dec;170(6):784-93. doi: 10.1667/RR1375.1.
3
Single-strand annealing, conservative homologous recombination, nonhomologous DNA end joining, and the cell cycle-dependent repair of DNA double-strand breaks induced by sparsely or densely ionizing radiation.单链退火、保守同源重组、非同源DNA末端连接以及由稀疏或密集电离辐射诱导的DNA双链断裂的细胞周期依赖性修复。
Radiat Res. 2009 Mar;171(3):265-73. doi: 10.1667/RR0784.1.
4
Repair of DNA double-strand breaks by mammalian alternative end-joining pathways.哺乳动物非同源末端连接途径修复 DNA 双链断裂。
J Biol Chem. 2018 Jul 6;293(27):10536-10546. doi: 10.1074/jbc.TM117.000375. Epub 2018 Mar 12.
5
Repair pathway choice for double-strand breaks.双链断裂的修复途径选择。
Essays Biochem. 2020 Oct 26;64(5):765-777. doi: 10.1042/EBC20200007.
6
Increased Gene Targeting in Hyper-Recombinogenic LymphoBlastoid Cell Lines Leaves Unchanged DSB Processing by Homologous Recombination.高重组性淋巴母细胞系中基因靶向增加，同源重组的 DSB 处理不变。
Int J Mol Sci. 2022 Aug 16;23(16):9180. doi: 10.3390/ijms23169180.
7
The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks.电离辐射诱导的 DNA 双链断裂中 DNA 修复途径选择的决定因素。
Biomed Res Int. 2020 Aug 25;2020:4834965. doi: 10.1155/2020/4834965. eCollection 2020.
8
Regulation of DNA double-strand break repair pathway choice.DNA双链断裂修复途径选择的调控
Cell Res. 2008 Jan;18(1):134-47. doi: 10.1038/cr.2007.111.
9
Repair Pathway Choices and Consequences at the Double-Strand Break.双链断裂处的修复途径选择及其后果
Trends Cell Biol. 2016 Jan;26(1):52-64. doi: 10.1016/j.tcb.2015.07.009. Epub 2015 Oct 1.
10
Ubiquitylation in DNA double-strand break repair.泛素化在 DNA 双链断裂修复中的作用。
DNA Repair (Amst). 2021 Jul;103:103129. doi: 10.1016/j.dnarep.2021.103129. Epub 2021 May 7.
引用本文的文献
1
The distinct landscape of tumor immune microenvironment in homologous recombination deficient cancers.同源重组缺陷型癌症中独特的肿瘤免疫微环境格局。
Biomark Res. 2025 Aug 20;13(1):108. doi: 10.1186/s40364-025-00814-x.
2
Comprehensive computational analysis via Adverse Outcome Pathways and Aggregate Exposure Pathways in exploring synergistic effects from radon and tobacco smoke on lung cancer.通过不良结局途径和累积暴露途径进行综合计算分析，以探索氡气和烟草烟雾对肺癌的协同作用。
Front Public Health. 2025 Jul 31;13:1571290. doi: 10.3389/fpubh.2025.1571290. eCollection 2025.
3
Radiation Therapy Personalization in Cancer Treatment: Strategies and Perspectives.癌症治疗中的放射治疗个体化：策略与展望
Int J Mol Sci. 2025 Jul 2;26(13):6375. doi: 10.3390/ijms26136375.
4
Revisiting Genomic Instability, Tumor Microenvironment and Immune Response in High-Grade Serous Ovarian Cancer.重新审视高级别浆液性卵巢癌中的基因组不稳定性、肿瘤微环境和免疫反应
Geburtshilfe Frauenheilkd. 2025 Jun 11;85(7):694-709. doi: 10.1055/a-2613-0489. eCollection 2025 Jul.
5
DNA repair and the contribution to chemotherapy resistance.DNA修复及其对化疗耐药性的影响。
Genome Med. 2025 May 26;17(1):62. doi: 10.1186/s13073-025-01488-8.
6
TOX High-Mobility Group Box Family Member 4 promotes DNA double-strand break repair via nonhomologous end joining.TOX高迁移率族盒蛋白家族成员4通过非同源末端连接促进DNA双链断裂修复。
J Biol Chem. 2025 May 4;301(6):110174. doi: 10.1016/j.jbc.2025.110174.
7
Mutant p53 upregulates HDAC6 to resist ER stress and facilitates Ku70 deacetylation, which prevents its degradation and mitigates DNA damage in colon cancer cells.突变型p53上调HDAC6以抵抗内质网应激，并促进Ku70去乙酰化，从而防止其降解并减轻结肠癌细胞中的DNA损伤。
Cell Death Discov. 2025 Apr 10;11(1):162. doi: 10.1038/s41420-025-02433-9.
8
BRCA2-Related Hereditary Cancer Syndrome-Associated Small Bowel Adenocarcinoma With Multiple BRCA2 Mutations: A Case Report and Review of the Literature.与BRCA2相关的遗传性癌症综合征相关的小肠腺癌伴多个BRCA2突变：病例报告及文献复习
Cancer Rep (Hoboken). 2025 Apr;8(4):e70200. doi: 10.1002/cnr2.70200.
9
Homeodomain protein PRRX1 anchors the Ku heterodimers at DNA double-strand breaks to promote nonhomologous end-joining.同源结构域蛋白PRRX1将Ku异源二聚体锚定在DNA双链断裂处，以促进非同源末端连接。
Nucleic Acids Res. 2025 Mar 20;53(6). doi: 10.1093/nar/gkaf200.
10
Disruption of mitochondrial DNA integrity in cardiomyocyte injury upon ischemia/reperfusion.缺血/再灌注时心肌细胞损伤中线粒体DNA完整性的破坏。
Genes Dis. 2024 Mar 28;12(3):101282. doi: 10.1016/j.gendis.2024.101282. eCollection 2025 May.
本文引用的文献
1
DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions.DNA 双链断裂反应因子影响 IgH 类别转换和一般易位连接点的连接特征。
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):762-767. doi: 10.1073/pnas.1719988115. Epub 2018 Jan 8.
2
Nonhomologous DNA end-joining for repair of DNA double-strand breaks.非同源 DNA 末端连接修复 DNA 双链断裂。
J Biol Chem. 2018 Jul 6;293(27):10512-10523. doi: 10.1074/jbc.TM117.000374. Epub 2017 Dec 14.
3
Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair.细胞周期依赖性磷酸化调节 RECQL4 途径选择和 DNA 双链断裂修复中的泛素化。
Nat Commun. 2017 Dec 11;8(1):2039. doi: 10.1038/s41467-017-02146-3.
4
Acetylation of 53BP1 dictates the DNA double strand break repair pathway.53BP1 的乙酰化决定了 DNA 双链断裂修复途径。
Nucleic Acids Res. 2018 Jan 25;46(2):689-703. doi: 10.1093/nar/gkx1208.
5
Differentiation of Human Induced Pluripotent or Embryonic Stem Cells Decreases the DNA Damage Repair by Homologous Recombination.人类诱导多能干细胞或胚胎干细胞的分化会降低同源重组的 DNA 损伤修复。
Stem Cell Reports. 2017 Nov 14;9(5):1660-1674. doi: 10.1016/j.stemcr.2017.10.002. Epub 2017 Nov 2.
6
The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.Polθ的解旋酶结构域可对抗RPA以促进替代性非同源末端连接。
Nat Struct Mol Biol. 2017 Dec;24(12):1116-1123. doi: 10.1038/nsmb.3494. Epub 2017 Oct 23.
7
AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway.AUNIP/C1orf135将DNA双链断裂导向同源重组修复途径。
Nat Commun. 2017 Oct 17;8(1):985. doi: 10.1038/s41467-017-01151-w.
8
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN.NHEJ抑制剂CYREN对S期和G2期DNA修复途径选择的调控
Nature. 2017 Sep 20;549(7673):548-552. doi: 10.1038/nature24023.
9
SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination.SAMHD1 通过促进 DNA 末端切除来促进同源重组修复 DNA。
Cell Rep. 2017 Aug 22;20(8):1921-1935. doi: 10.1016/j.celrep.2017.08.008.
10
DNA end resection requires constitutive sumoylation of CtIP by CBX4.DNA 末端切除需要 CBX4 对 CtIP 进行组成型 SUMO 化修饰。
Nat Commun. 2017 Jul 24;8(1):113. doi: 10.1038/s41467-017-00183-6.
Zotero 插件