Rad51 Nuclear(Rad51 核)研究综述
Rad51 Nuclear Rad51 核 - In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. [1] E2F1 knockdown inhibited RAD51 nuclear foci formation after acute particulate Cr(VI) exposure. [2] In conclusion, we demonstrated for the first time that CD81 not only played a vital role in DNA repair through regulating Rad51 nuclear transport, but also might serve as a potential target of GBM radiotherapy. [3] This is because PUMA can be associated with early mitotic inhibitor 1 (EMI1) and Rad51 in the cytoplasm to facilitate EMI1-mediated cytoplasmic Rad51 ubiquitination and degradation, thereby inhibiting Rad51 nuclear translocation and HR DNA repair. [4] Treatment with the CDK4/6 inhibitor palbociclib led to downregulation of MYC-regulated HR repair pathway genes as well as reduced RAD51 nuclear foci (a marker for the competency of homologous recombination repair) but increased γH2AX nuclear foci formation (a surrogate marker for DNA double strand breaks) in those ovarian cancer cell lines that demonstrated synergistic interactions to combined treatment with the PARP inhibitor olaparib and the CDK4/6 inhibitor palbociclib. [5] Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hypersensitivity to mitomycin C and olaparib. [6] Levels exceeding 4% nuclear area positive (NAP) γH2AX, 4% NAP pS343-Nbs1, and 5% cells with ≥5 Rad51 nuclear foci indicate a DDR activation response to treatment in human colorectal cancer tissue. [7] To validate the DNA repair proficiency of the transformed cells, we measured Rad51 nuclear focus formation after ionizing radiation (IR) and PARP inhibitor and DNA-damaging agent sensitivity. [8] Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hyper-sensitivity to mitomycin C and olaparib, with the weakest phenotypes observed in RAD51B-deficient cells. [9] Moreover, BRAFi impaired global DNA repair and altered the resolution of 53BP1 and RAD51 nuclear foci in BRAFV600E cells following IR. [10]在细胞中，CAM833 减少了损伤诱导的 RAD51 核灶的形成；抑制 RAD51 分子聚集，抑制扩展的 RAD51 细丝组装；通过电离辐射增强细胞毒性，增加 4N 细胞周期停滞和细胞凋亡，并与聚 ADP 核糖聚合酶 (PARP)1 抑制剂一起抑制 BRCA2 野生型细胞的生长。 [1] E2F1 组合式抑制急性颗粒 Cr(VI) 暴露后 RAD51 核病灶形成。 [2] 总之，我们首次证明CD81不仅通过调节Rad51核转运在DNA修复中发挥重要作用，而且可能作为GBM放射治疗的潜在靶点。 [3] 这是因为 PUMA 可以与细胞质中的早期有丝分裂抑制剂 1 (EMI1) 和 Rad51 结合，促进 EMI1 介导的细胞质 Rad51 泛素化和降解，从而抑制 Rad51 核转位和 HR DNA 修复。 [4] 用 CDK4/6 抑制剂 palbociclib 治疗导致 MYC 调节的 HR 修复途径基因的下调以及 RAD51 核病灶（同源重组修复能力的标志物）减少，但 γH2AX 核病灶形成增加（DNA 双的替代标志物）链断裂）在卵巢癌细胞系中显示出与 PARP 抑制剂 olaparib 和 CDK4/6 抑制剂 palbociclib 联合治疗的协同相互作用。 [5] 强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼过敏。 [6] 超过 4% 核面积阳性 (NAP) γH2AX、4% NAP pS343-Nbs1 和 5% 具有 ≥5 Rad51 核灶的细胞表明 DDR 激活对人结直肠癌组织治疗的反应。 [7] 为了验证转化细胞的 DNA 修复能力，我们测量了电离辐射 (IR) 和 PARP 抑制剂和 DNA 损伤剂敏感性后的 Rad51 核焦点形成。 [8] 强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼的超敏性，在 RAD51B 缺陷细胞中观察到最弱的表型。 [9] 此外，BRAFi 损害了全球 DNA 修复并改变了 IR 后 BRAFV600E 细胞中 53BP1 和 RAD51 核灶的分辨率。 [10]
Stable Rad51 Nuclear
Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hypersensitivity to mitomycin C and olaparib. [1] Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hyper-sensitivity to mitomycin C and olaparib, with the weakest phenotypes observed in RAD51B-deficient cells. [2]强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼过敏。 [1] 强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼的超敏性，在 RAD51B 缺陷细胞中观察到最弱的表型。 [2]
rad51 nuclear focus Rad51 核焦点
In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. [1] E2F1 knockdown inhibited RAD51 nuclear foci formation after acute particulate Cr(VI) exposure. [2] Treatment with the CDK4/6 inhibitor palbociclib led to downregulation of MYC-regulated HR repair pathway genes as well as reduced RAD51 nuclear foci (a marker for the competency of homologous recombination repair) but increased γH2AX nuclear foci formation (a surrogate marker for DNA double strand breaks) in those ovarian cancer cell lines that demonstrated synergistic interactions to combined treatment with the PARP inhibitor olaparib and the CDK4/6 inhibitor palbociclib. [3] Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hypersensitivity to mitomycin C and olaparib. [4] Levels exceeding 4% nuclear area positive (NAP) γH2AX, 4% NAP pS343-Nbs1, and 5% cells with ≥5 Rad51 nuclear foci indicate a DDR activation response to treatment in human colorectal cancer tissue. [5] Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hyper-sensitivity to mitomycin C and olaparib, with the weakest phenotypes observed in RAD51B-deficient cells. [6] Moreover, BRAFi impaired global DNA repair and altered the resolution of 53BP1 and RAD51 nuclear foci in BRAFV600E cells following IR. [7]在细胞中，CAM833 减少了损伤诱导的 RAD51 核灶的形成；抑制 RAD51 分子聚集，抑制扩展的 RAD51 细丝组装；通过电离辐射增强细胞毒性，增加 4N 细胞周期停滞和细胞凋亡，并与聚 ADP 核糖聚合酶 (PARP)1 抑制剂一起抑制 BRCA2 野生型细胞的生长。 [1] E2F1 组合式抑制急性颗粒 Cr(VI) 暴露后 RAD51 核病灶形成。 [2] 用 CDK4/6 抑制剂 palbociclib 治疗导致 MYC 调节的 HR 修复途径基因的下调以及 RAD51 核病灶（同源重组修复能力的标志物）减少，但 γH2AX 核病灶形成增加（DNA 双的替代标志物）链断裂）在卵巢癌细胞系中显示出与 PARP 抑制剂 olaparib 和 CDK4/6 抑制剂 palbociclib 联合治疗的协同相互作用。 [3] 强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼过敏。 [4] 超过 4% 核面积阳性 (NAP) γH2AX、4% NAP pS343-Nbs1 和 5% 具有 ≥5 Rad51 核灶的细胞表明 DDR 激活对人结直肠癌组织治疗的反应。 [5] 强调它们对基因组稳定性的重要性，突变细胞系显示出可变的生长缺陷、受损的姐妹染色单体重组、稳定的 RAD51 核病灶水平降低以及对丝裂霉素 C 和奥拉帕尼的超敏性，在 RAD51B 缺陷细胞中观察到最弱的表型。 [6] 此外，BRAFi 损害了全球 DNA 修复并改变了 IR 后 BRAFV600E 细胞中 53BP1 和 RAD51 核灶的分辨率。 [7]