选择正确的道路：DNA-PK 是否有助于做出决策？
Choosing the right path: does DNA-PK help make the decision?
机构信息
College of Veterinary Medicine, Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, United States.
出版信息
Mutat Res. 2011 Jun 3;711(1-2):73-86. doi: 10.1016/j.mrfmmm.2011.02.010. Epub 2011 Mar 3.
Abstract
DNA double-strand breaks are extremely harmful lesions that can lead to genomic instability and cell death if not properly repaired. There are at least three pathways that are responsible for repairing DNA double-strand breaks in mammalian cells: non-homologous end joining, homologous recombination and alternative non-homologous end joining. Here we review each of these three pathways with an emphasis on the role of the DNA-dependent protein kinase, a critical component of the non-homologous end joining pathway, in influencing which pathway is ultimately utilized for repair.
摘要
DNA 双链断裂是极其有害的损伤，如果不能得到妥善修复，可能导致基因组不稳定和细胞死亡。哺乳动物细胞中至少有三种途径负责修复 DNA 双链断裂：非同源末端连接、同源重组和替代性非同源末端连接。本文重点介绍了非同源末端连接途径中的关键组成部分——依赖于 DNA 的蛋白激酶，综述了这三种途径，并讨论了其对最终修复途径选择的影响。
相似文献
1
Choosing the right path: does DNA-PK help make the decision?选择正确的道路：DNA-PK 是否有助于做出决策？
Mutat Res. 2011 Jun 3;711(1-2):73-86. doi: 10.1016/j.mrfmmm.2011.02.010. Epub 2011 Mar 3.
2
Extensive ssDNA end formation at DNA double-strand breaks in non-homologous end-joining deficient cells during the S phase.在S期，非同源末端连接缺陷细胞中DNA双链断裂处广泛形成单链DNA末端。
BMC Mol Biol. 2007 Oct 26;8:97. doi: 10.1186/1471-2199-8-97.
3
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.
4
Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.Ku 调控人源体细胞 DNA 双链断裂修复的非同源末端连接途径选择。
PLoS Genet. 2010 Feb 26;6(2):e1000855. doi: 10.1371/journal.pgen.1000855.
5
Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.通过非同源末端连接修复电离辐射诱导的DNA双链断裂。
Biochem J. 2009 Feb 1;417(3):639-50. doi: 10.1042/BJ20080413.
6
DNA-PK: a dynamic enzyme in a versatile DSB repair pathway.DNA-PK：一种在多种 DSB 修复途径中发挥作用的动态酶。
DNA Repair (Amst). 2014 May;17:21-9. doi: 10.1016/j.dnarep.2014.02.020. Epub 2014 Mar 27.
7
Detection and repair of ionizing radiation-induced DNA double strand breaks: new developments in nonhomologous end joining.检测和修复电离辐射诱导的 DNA 双链断裂：非同源末端连接的新进展。
Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):440-9. doi: 10.1016/j.ijrobp.2013.01.011. Epub 2013 Feb 20.
8
DNA-PK-dependent phosphorylation of Ku70/80 is not required for non-homologous end joining.非同源末端连接不需要DNA-PK依赖的Ku70/80磷酸化。
DNA Repair (Amst). 2005 Aug 15;4(9):1006-18. doi: 10.1016/j.dnarep.2005.05.003.
9
Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells.非同源末端连接是哺乳动物细胞中修复氟达拉滨诱导的DNA双链断裂的相关途径。
Mutat Res. 2008 Nov 10;646(1-2):8-16. doi: 10.1016/j.mrfmmm.2008.08.013. Epub 2008 Sep 4.
10
Repair of DNA double strand breaks by non-homologous end joining.通过非同源末端连接修复DNA双链断裂
Biochimie. 2003 Nov;85(11):1161-73. doi: 10.1016/j.biochi.2003.10.011.
引用本文的文献
1
Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.作为潜在癌症治疗药物的ATM、ATR和DNA-PK抑制剂的药物化学突破。
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2489720. doi: 10.1080/14756366.2025.2489720. Epub 2025 Apr 21.
2
Alpha-synuclein modulates the repair of genomic DNA double-strand breaks in a DNA-PK-regulated manner.α-突触核蛋白以依赖于 DNA-PK 的方式调节基因组 DNA 双链断裂的修复。
Neurobiol Dis. 2024 Oct 15;201:106675. doi: 10.1016/j.nbd.2024.106675. Epub 2024 Sep 19.
3
BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.BUB1 通过调控非同源末端连接通路介导三阴性乳腺癌放射抵抗。
J Exp Clin Cancer Res. 2024 Jun 11;43(1):163. doi: 10.1186/s13046-024-03086-9.
4
Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.肿瘤坏死因子-α对PRKDC的非常规激活：解析其作为DNA-PK复合物一部分在Th1介导的炎症中超越DNA修复的关键作用。
J Inflamm (Lond). 2024 Apr 30;21(1):14. doi: 10.1186/s12950-024-00386-x.
5
Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.通过DNA-PKcs激酶活性对基础状态和依托泊苷诱导的基因表达变化进行比较分析。
Front Genet. 2024 Mar 21;15:1276365. doi: 10.3389/fgene.2024.1276365. eCollection 2024.
6
Targeting DNA-PK.靶向 DNA-PK
Cancer Treat Res. 2023;186:299-312. doi: 10.1007/978-3-031-30065-3_16.
7
Dose-Dependent Shift in Relative Contribution of Homologous Recombination to DNA Repair after Low-LET Ionizing Radiation Exposure: Empirical Evidence and Numerical Simulation.低传能线密度电离辐射暴露后同源重组对DNA修复相对贡献的剂量依赖性变化：实验证据与数值模拟
Curr Issues Mol Biol. 2023 Sep 9;45(9):7352-7373. doi: 10.3390/cimb45090465.
8
The Influence of Edaphic Factors on DNA Damage and Repair in Wild Wheat Körn. (, Triticeae).土壤因素对野生小麦 Körn. （，小麦族）DNA 损伤与修复的影响。
Int J Mol Sci. 2023 Apr 6;24(7):6847. doi: 10.3390/ijms24076847.
9
DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells.牛卵丘细胞中与 DNA 双链断裂相关的非编码 RNA 竞争性内源性 RNA 网络。
Genes (Basel). 2023 Jan 22;14(2):290. doi: 10.3390/genes14020290.
10
Increased Resection at DSBs in G-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ.在 G 期时 DSBs 的增加切除是与 DNA-PKcs 缺陷相关的独特表型，而与其他 c-NHEJ 因子无关。
Cells. 2022 Jul 2;11(13):2099. doi: 10.3390/cells11132099.
本文引用的文献
1
Factors determining DNA double-strand break repair pathway choice in G2 phase.决定 G2 期 DNA 双链断裂修复途径选择的因素。
EMBO J. 2011 Mar 16;30(6):1079-92. doi: 10.1038/emboj.2011.27. Epub 2011 Feb 11.
2
Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation.DNA 依赖性蛋白激酶对同源重组的抑制需要激酶活性，是可滴定的，并受自身磷酸化调节。
Mol Cell Biol. 2011 Apr;31(8):1719-33. doi: 10.1128/MCB.01298-10. Epub 2011 Feb 7.
3
ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks.ATM 损伤反应和 XLF 修复因子在连接 DNA 断裂中具有功能冗余性。
Nature. 2011 Jan 13;469(7329):250-4. doi: 10.1038/nature09604. Epub 2010 Dec 15.
4
A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation.DNA-PKcs 自磷酸化调控 NHEJ 的结构模型。
DNA Repair (Amst). 2010 Dec 10;9(12):1307-14. doi: 10.1016/j.dnarep.2010.09.019. Epub 2010 Oct 28.
5
The DNA damage response: making it safe to play with knives.DNA 损伤反应：让“玩刀”变得安全。
Mol Cell. 2010 Oct 22;40(2):179-204. doi: 10.1016/j.molcel.2010.09.019.
6
Structural biology of DNA repair: spatial organisation of the multicomponent complexes of nonhomologous end joining.DNA修复的结构生物学：非同源末端连接多组分复合物的空间组织
J Nucleic Acids. 2010 Aug 25;2010:621695. doi: 10.4061/2010/621695.
7
Dual modes of interaction between XRCC4 and polynucleotide kinase/phosphatase: implications for nonhomologous end joining.XRCC4 与多核苷酸激酶/磷酸酶的两种相互作用模式：对非同源末端连接的影响。
J Biol Chem. 2010 Nov 26;285(48):37619-29. doi: 10.1074/jbc.M109.058719. Epub 2010 Sep 17.
8
Purified human BRCA2 stimulates RAD51-mediated recombination.纯化的人源 BRCA2 可刺激 RAD51 介导的重组。
Nature. 2010 Oct 7;467(7316):678-83. doi: 10.1038/nature09399.
9
The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers.机械因素在促进淋巴和其他癌症中发现的染色体易位中的作用。
Adv Immunol. 2010;106:93-133. doi: 10.1016/S0065-2776(10)06004-9.
10
Coordination of DNA-PK activation and nuclease processing of DNA termini in NHEJ.在 NHEJ 中，DNA-PK 的激活和 DNA 末端核酸酶加工的协调作用。
Antioxid Redox Signal. 2011 Jun 15;14(12):2531-43. doi: 10.1089/ars.2010.3368. Epub 2010 Dec 2.
Zotero 插件