Добірка наукової літератури з теми "KU70 gene"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся зі списками актуальних статей, книг, дисертацій, тез та інших наукових джерел на тему "KU70 gene".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Статті в журналах з теми "KU70 gene"
1
Ouyang, Honghai, Andre Nussenzweig, Akihiro Kurimasa, Vera da Costa Soares, Xiaoling Li, Carlos Cordon-Cardo, Wen-hui Li, et al. "Ku70 Is Required for DNA Repair but Not for T Cell Antigen Receptor Gene Recombination In Vivo." Journal of Experimental Medicine 186, no. 6 (September 15, 1997): 921–29. http://dx.doi.org/10.1084/jem.186.6.921.
Повний текст джерелаАнотація:
Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70−/−). Like Ku80−/− mice, Ku70−/− mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80−/− mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8− and CD4−CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.
2
Li, Han, Hannes Vogel, Valerie B. Holcomb, Yansong Gu, and Paul Hasty. "Deletion of Ku70, Ku80, or Both Causes Early Aging without Substantially Increased Cancer." Molecular and Cellular Biology 27, no. 23 (September 17, 2007): 8205–14. http://dx.doi.org/10.1128/mcb.00785-07.
Повний текст джерелаАнотація:
ABSTRACT Ku70 forms a heterodimer with Ku80, called Ku, that is critical for repairing DNA double-stand breaks by nonhomologous end joining and for maintaining telomeres. Mice with either gene mutated exhibit similar phenotypes that include increased sensitivity to ionizing radiation and severe combined immunodeficiency. However, there are also differences in the reported phenotypes. For example, only Ku70 mutants are reported to exhibit a high incidence of thymic lymphomas while only Ku80 mutants are reported to exhibit early aging with very low cancer levels. There are two explanations for these differences. First, either Ku70 or Ku80 functions outside the Ku heterodimer such that deletion of one is not identical to deletion of the other. Second, divergent genetic backgrounds or environments influence the phenotype. To distinguish between these possibilities, the Ku70 and Ku80 mutations were crossed together to generate Ku70, Ku80, and double-mutant mice in the same genetic background raised in the same environment. We show that these three cohorts have similar phenotypes that most resemble the previous report for Ku80 mutant mice, i.e., early aging without substantially increased cancer levels. Thus, our observations suggest that the Ku heterodimer is important for longevity assurance in mice since divergent genetic backgrounds and/or environments likely account for these previously reported differences.
3
Sucharov, Carmen C., Steve M. Helmke, Stephen J. Langer, M. Benjamin Perryman, Michael Bristow та Leslie Leinwand. "The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression". Molecular and Cellular Biology 24, № 19 (1 жовтня 2004): 8705–15. http://dx.doi.org/10.1128/mcb.24.19.8705-8715.2004.
Повний текст джерелаАнотація:
ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.
4
Weterings, Eric, Nicole S. Verkaik, Guido Keijzers, Bogdan I. Florea, Shih-Ya Wang, Laura G. Ortega, Naoya Uematsu, David J. Chen, and Dik C. van Gent. "The Ku80 Carboxy Terminus Stimulates Joining and Artemis-Mediated Processing of DNA Ends." Molecular and Cellular Biology 29, no. 5 (December 22, 2008): 1134–42. http://dx.doi.org/10.1128/mcb.00971-08.
Повний текст джерелаАнотація:
ABSTRACT Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA-PKCS) and the XRCC4/ligase IV complex. Activation of the DNA-PKCS serine/threonine kinase requires an interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In contrast to previous models, we found that the carboxy terminus of Ku80 is not absolutely required for the recruitment and activation of DNA-PKCS at DSBs, although cells that harbored a carboxy-terminal deletion in the Ku80 gene were sensitive to ionizing radiation and showed reduced end-joining capacity. More detailed analysis of this repair defect showed that DNA-PKCS autophosphorylation at Thr2647 was diminished, while Ser2056 was phosphorylated to normal levels. This resulted in severely reduced levels of Artemis nuclease activity in vivo and in vitro. We therefore conclude that the Ku80 carboxy terminus is important to support DNA-PKCS autophosphorylation at specific sites, which facilitates DNA end processing by the Artemis endonuclease and the subsequent joining reaction.
5
Ghonim, Mohamed Ahmed, Kusma Pyakurel, Hanh Luu, Samuel Okpechi, Jihang Ju, and Hamid Boulares. "The catalytic subunit of DNA-PK has a unique function in inflammation independently of Ku70 and DNA repair: a new opportunity to target the enzyme without interfering with DNA repair." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 173.18. http://dx.doi.org/10.4049/jimmunol.200.supp.173.18.
Повний текст джерелаАнотація:
Abstract Our laboratory demonstrated a critical role for DNA-dependent protein kinase (DNA-PK) in asthma pathogenesis via modulating the pertinent immune responses. DNA-PK is DNA repair enzyme composed of a catalytic subunit (DNA-PKcs) and two DNA-binding subunits (Ku70 and Ku80). Human cells express high levels of DNA-PK, surprisingly such high levels do not confer increased ability to repair DNA damage. Here we show that the role of DNA-PK in promoting inflammatory responses is independent of its function in the DNA repair. We examined the effect(s) of partial depletion of Ku70 on Ovalbumin (OVA) induced lung inflammation in mouse model of the disease. Of note, depletion of Ku70 by gene heterozygosity causes deficiency in DNA-PK-dependent DNA repair. Unlike the protective effects provided by DNA-PKcs gene heterozygosity, Ku70 heterozygosity did not alter the OVA-induced eosinophilia, mucus hypersecretion, Th2 cytokines production, or OVA-specific IgE upon OVA challenge. Interestingly, Ku70 heterozygosity enhanced methacholine-induced AHR over that of WT mice. Using a cell culture system, we demonstrate that while IL-4 and TNF-α are potent inducers of DNA-PKcs, such activation did not coincide with any detectable DNA damage or repair responses. Remarkably, while Ku70−/− blocked DNA-PKcs autophosphorylation in response to the DNA damage agent, etoposide, it did not affect the kinase in response to TNFα. Our findings suggest that the mechanism by which DNA-PK functions in inflammation is completely unrelated to its role in DNA repair, thus, unraveling a completely novel function for the kinase. More importantly, this provides a window of opportunity to target DNA-PK in inflammatory diseases without interfering with DNA repair processes.
6
Fu, Chengcheng, Peishuai Chen, Wu Depei, and Zixing Chen. "Study of Expression of Ku70 and NHEJ in CML Cells." Blood 112, no. 11 (November 16, 2008): 3223. http://dx.doi.org/10.1182/blood.v112.11.3223.3223.
Повний текст джерелаАнотація:
Abstract Objective FThe DNA double strand breaks (DSB) in mammalian cells are predominantly repaired by a process called non-homologous DNA end joining (NHEJ). Ku70 played a pivotal role in NHEJ pathway. As a common hematological malignant disease with unique chromosomal translocation t (9;22), chronic myeloid leukemia (CML) can be considered as a paradigm for neoplasias that evolve through a multi-step process. As we reported before, protein Ku70 expressed significantly higher in CML than in normal BM cells. Meanwhile, its expression level in blast phase was markedly higher than that in chronic phase. The present study furthermore aims to investigate the expression of the gene Ku70 in CML cells at different clinical stage and reveal the correlation among the expression of the gene Ku70, the protein Ku70 and BCR-ABL in cells of CML. The NHEJ efficiency to repair DSB in CML was also investigated. Methods: Bone marrow cells were collected from 24 cases of normal adults and 27 cases of de novo diagnosed CML patients. 15 CML patients were in chronic phase and 12 in blast phase. The expression of gene Ku70 was detected by RT-PCR and RQ-RT-PCR. The fusion gene BCR-ABL was detected by TaqMan probe Real Time PCR, using ABL as the internal control. Nucleic extracted proteins were used to determine NHEJ efficiency by an in vitro end-ligation system. Results: The mean level of NHEJ activity of normal BM cells and CML cells were 18.6±13.1% vs 24.8±14.9%, .024. The gene Ku 70 expression in normal BM cells and CML cells were 31.08±8.41 vs 544.63±1185.71 copies/10,000 β-Actin copies, P=0.039. gene Ku 70 expressed significantly higher in blast phase (1103.31±1645.62 copies/10,000 β-Actin copies, P<0.01). There were positive correlations of BCR-ABL when compared with the expression of the gene Ku70 (r=0.573 P=0.002) and with the protein Ku70 (r=0.705 P<0.001) in CML cells. There was also significantly correlations between the expression of the gene Ku70 and the protein Ku70 (r=0. 808, P<0.001). Conclusions: The gene and protein of Ku70 were expressed significantly higher in CML than in normal BM cells with NHEJ activity was also enhanced in CML cells. Meanwhile, Ku70 expression level in acute phase was markedly higher than that in chronic phase. There were significantly correlations among the expression of fusion gene BCR-ABL, the gene Ku70 and the protein Ku70 in cells of CML This Study illustrates DNA instability in CML cells which was mainly damaged by DSB, and this kind of DNA damage was repaired by NHEJ pathway predominantly. NHEJ pathway plays an important role in disease progression of CML.
7
Gao, Chao, Guangxu Jin, Elizabeth Forbes, Lingegowda S. Mangala, Yingmei Wang, Cristian Rodriguez-Aguayo, Paola Amero, et al. "Inactivating Mutations of the IK Gene Weaken Ku80/Ku70-Mediated DNA Repair and Sensitize Endometrial Cancer to Chemotherapy." Cancers 13, no. 10 (May 20, 2021): 2487. http://dx.doi.org/10.3390/cancers13102487.
Повний текст джерелаАнотація:
IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK’s role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.
8
Imamichi, Tomozumi, Xing Zhang, Ming Zhou, Richard Lempicki, Michael Baseler, Timothy Veenstra, Howard Young, and H. Clifford Lane. "Ku70 is a novel cytosolic DNA sensor that induces a Type-III rather than Type-I IFN via activation of IRF-1 and IRF-7. (116.11)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 116.11. http://dx.doi.org/10.4049/jimmunol.186.supp.116.11.
Повний текст джерелаАнотація:
Abstract Recent studies have demonstrated that foreign cytoplasmic DNA is detected by cytosolic DNA sensors (DAI, AIM-2, LRRFIP1, RNA polymerase III, or IFI16) that induce Type-I IFN or IL-1β. We have previously found that HEK293 cell transfected with DNA induces a Type-III IFN (IFN-λ1) rather than Type-I IFN. In this study, utilizing a pull down assay followed by mass spectrometry, we identified the DNA sensor protein that specifically induces IFN-λ1. Changes in expression level of gene and protein were evaluated by real time RT-PCR and Western blot. Transfection of not only plasmid DNA but also PCR amplified DNA and bacteria DNA induced IFN-λ1 activation in cell lines, primary macrophages and dendritic cells. DNA virus (HSV-2) infection also induced IFN-λ1 production. The pull down assay using DNA-beads resulted in that DNA-binding proteins in cytosole were Ku70 and Ku80, a DNA repair protein, as playing potentially important role. Knockdown of Ku70, but not Ku80, by siRNA led to 90% and 70% reduction in the DNA- and the virus-mediated IFN-λ1 induction, respectively. Over expression of Ku70 induced activation of the IFN-λ1 promoter. DNA binding assay using NFκB-, ISRE- or PRDI-beads with nuclear extract from DNA transfected cells indicated that the DNA-mediated IFN-λ1 induction was associated with the activation of IRF-1 and IRF-7 rather than IRF-3 and NFκB. Taken together; these data demonstrated that Ku70 exerts a novel cytosolic DNA sensor that specifically activates IFN-λ1.
9
Koh, Chong Mei, Yanbin Liu, Moehninsi, Minge Du, and Lianghui Ji. "Molecular characterization of KU70 and KU80 homologues and exploitation of a KU70-deficient mutant for improving gene deletion frequency in Rhodosporidium toruloides." BMC Microbiology 14, no. 1 (2014): 50. http://dx.doi.org/10.1186/1471-2180-14-50.
Повний текст джерела
10
Qing, Yulan, Zhengqi Wang, Shigemi Matsuyama, Kevin D. Bunting, and Stanton L. Gerson. "Rescue of the HSC Maintenance Defects in Ku70-Deficient Mice by Overexpression of Bcl2 Reveals a Novel Role of Bcl2 in HSC." Blood 120, no. 21 (November 16, 2012): 1235. http://dx.doi.org/10.1182/blood.v120.21.1235.1235.
Повний текст джерелаАнотація:
Abstract Abstract 1235 Ku70 is a key component of the non-homologous end joining (NHEJ) pathway; Ku70-deficient mice are hypersensitive to radiation and show a leaky SCID phenotype. We find that HSC from Ku70-deficient mice are severely impaired in maintenance, defective in self-renewal, competitive repopulation and BM hematopoietic niche occupancy. HSCs from Ku70-deficient mice are not prone to spontaneous apoptosis, however, they display more active proliferation, and fewer cells in a quiescent state than HSC obtained from WT mice. Further, gene expression profiling showed that multiple HSC quiescence- related genes such as c-MPL and p57 were significantly downregulated in Ku70-deficient HSCs. These data suggested that loss of quiescence results in the dramatic defect in the maintenance of Ku70-deficient HSC. Bcl2 plays important roles in both anti-apoptosis and anti-proliferation, while the anti-apoptosis function of Bcl2 has been extensively studied and well established in various settings, including HSCs, the anti-proliferation function of Bcl2 in HSC has yet to be investigated. To exam whether overexpression of Bcl2 can rescue the HSC defect in Ku70-deficient mice, H2K-Bcl2 transgenic/Ku70-deficient double mutant mice were generated. Though overexpression of Bcl2 does not rescue the SCID phenotype in Ku70-deficient mice, overexpression of Bcl2 in Ku70-deficient HSCs almost completely rescued the impaired HSC quiescence, repopulation and BM hematopoietic niche occupancy capacities. At the transcriptional level, overexpression of Bcl2 restored the expression of c-MPL and p57 comparable to WT levels. However, additional deletion of Bax, a pro-apoptosis protein in the Bcl2 family, in Ku70-deficient mice could not rescue the HSC repopulation defect, suggesting that apoptosis is not the main mediator for the impaired HSC maintenance in Ku70-deficient mice. Together, our data indicate that the HSC maintenance defect of Ku70-deficient mice is due to the loss of HSC quiescence populations, whereas overexpression of Bcl2 rescues the HSC defect in Ku70-deficient mice by restoration of quiescence. Our study uncovers a novel role of Bcl2 in hematopoietic stem cell quiescence regulation. Disclosures: No relevant conflicts of interest to declare.
Дисертації з теми "KU70 gene"
1
Wickersham, Stephanie. "The down-regulation of Ku70, DNA-PKcs, and Parp-1 in mammalian cell lines." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2012, 2012. http://hdl.handle.net/10133/3401.
Повний текст джерелаАнотація:
DNA double strand breaks (DSBs) are primarily repaired in eukaryotic cells by two
different mechanisms – non-homologous end joining (NHEJ) or homologous
recombination (HR). In mammalian somatic cells the balance between the two highly
favours NHEJ. Gene targeting is a technique that exploits HR repair to alter a defined
gene locus. While it holds potential to be implemented as a treatment option for several
diseases, the outlook for using it in a clinical setting has been obstructed by a low gene
targeting efficiency. This has been coupled to the low frequency of HR in mammalian
cells. With the intention of shifting the repair balance, antibodies against DSB repair
proteins will be introduced into mammalian cells. It is predicted that by targeting key
repair proteins with antibodies, a compensatory increase in the frequency of HR can be
fostered, ultimately resulting in improved gene targeting.xv, 168 leaves : ill. ; 29 cm
2
Ghezzi, Tiago Leal. "Comparação da expressão gênica do KRAS mutante, KU70, TACSTD2 e SERIN1 em tecidos tumoral e normal de pacientes com câncer colorretal pela técnica de PCR em tempo real." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/22996.
Повний текст джерелаАнотація:
INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real.INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.
3
Mo, Wanbin [Verfasser]. "The Expression and Significance of MGMT, Ku80 and Ki67 Gene in Different Grades of Spinal gliomas / Wanbin Mo." Kiel : Universitätsbibliothek Kiel, 2015. http://d-nb.info/1069814636/34.
Повний текст джерела
4
Ghosh, Dipayan. "Understanding Nonhomologous DNA End Joining: Novel Insights Into Mechanism and Regulation." Thesis, 2022. https://etd.iisc.ac.in/handle/2005/5847.
Повний текст джерелаАнотація:
This study has provided new insights into the mechanistic details of NHEJ
and showed that DNA sequence around the break site can be a factor in determining which
proteins involved in NHEJ might be recruited with a higher efficiency. We have also generated
a KU70-mutant Nalm6 cell line (N6-Ku70-2) using CRISPR-Cas9 genome editing technology
and explored the differences between these cells and WT Nalm6 cells in terms of cell
proliferation and DNA repair potential. Finally, we have investigated the importance of
RNASEH2A/RNASEH2B expression in the maintenance of proper DSB repair and cellular
viability in T-ALL cells.
5
Hua, Chialing, and 花嘉玲. "The role of Ku80 in DNA repair and gene regulation." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/12027820768391790114.
Повний текст джерелаАнотація:
碩士國立清華大學
輻射生物研究所
84
DNA雙股斷裂是當細胞遭到游離輻射照射時產生最嚴重的傷害.為了瞭解細 胞輻射敏感的機制,有一些游離輻射敏感的突變株,已從中國倉鼠卵巢野生 型K1細胞被篩選出來 .其中xrs5和xrs6已知缺失將DNA雙股斷裂重新連結 的能力,同時也對MMS, EMS,UV等DNA傷害劑敏感;除此之外在這些突變株中 有十一種基因的表現較差.從最近的研究推論xrs突變株缺乏 Ku蛋白質 的80kDa次單元及Ku蛋白質所具有與DNA端點結合的特性,在xrs突變株中表 現人類Ku80則可使此轉染細胞株之DEB活性與對游離輻射的抗性同時回復. 為了解DNA雙股斷裂的修復系統,本實驗室已由xrs6細胞株中篩選得到表型 自然回復株SR16,由先前的研究發現SR16對X-ray和UV具有抗性,然而卻對 MMS和EMS依然敏感;同時SR16細胞也具有DEB活性.本論文主要在探討 Ku蛋 白質是否參與MMS,EMS和UV所造成DNA傷害的修復路徑.人類Ku80互補DNA是 利用反轉錄及聚合酵素連鎖反應的方法獲得,此 cDNA接著被選殖於可在真 核生物系統表現選殖DNA的表現載體pcDNA3中,之後利用lipofection的方 法將此表現質體送入xrs6細胞中.利用G418篩選穩定的轉染細胞,並將之培 養成細胞株;將十二個獨立細胞株混合而成的混合細胞株對IR具較高之抗 性.以獨立細胞株中的x6hk803與混合細胞株進行之後的實驗顯示:雖然利 用北方墨點轉漬實驗在轉染細胞株中,無法檢測到 Ku80 mRNA的訊號,但可 藉由反轉錄及聚合酵素連鎖反應,偵測到轉染細胞株中有人類Ku80 mRNA表 現的情形.雖然利用西方墨點轉漬實驗在轉染細胞株中,無法檢測到Ku80蛋 白質的訊號,但可利用電泳泳動偏移測定偵測到 Ku80轉染細胞株中具Ku蛋 白質特有的DEB活性,故確知在x6hk803及mix transfectant中有Ku之表現 而且具生物活性.由細胞存活實驗中得知Ku80轉染細胞株對MMS和EMS具抗 性,但對UV敏感.本實驗也對Ku是否調控某些基因的表現加以探討.結果顯 示在xrs突變株中mRNA表現量較低的基因-B52與B29在Ku80轉染細胞中表現 仍然不佳;故 Ku蛋白質並不參與調控這些基因的表現.從本論文結果推論 Ku蛋白質參與X-ray,MMS,和EMS所造成DNA傷害的修復路徑;同時,參與另一 機制的分子具有與DNA free ends結合的能力,因為 SR16細胞對IR及UV具 抗性並具有DEB活性,但對 MMS和EMS依然敏感.
6
Ting, Hui-Min, and 丁慧敏. "A DNA Microarray Study of Global Gene Expression And Radiation biological Effects of Ku80 Gene Knockout Cells." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/42895551689872609697.
Повний текст джерелаАнотація:
碩士國立陽明大學
放射醫學科學研究所
90
DNA contains genetic information which is essential to the cell’s physiological mechanisms. In the event of DNA damage, repair mechanisms are activated in order to initiate pathways which will lead to repair of the damage, so as to avoid cell death, mutation and thus to preserve the integrity of the genome. Since DNA repair plays a vital role in the cell’s survival and consequently to the survival of the whole organism, we have chosen to study the Ku protein, which plays an important role in DNA double strand break repair particularly the non-homologous end rejoining repair mechanism. In this study, we used Ku80 knockout mouse embryo fibroblasts and its wild-type counterpart to study the differences in global gene expression between the two cell lines under irradiated or non-irradiated conditions. Survival dose response using colony formation showed high radiosensitivity of the knockout cells relative to the wild-type. Flow cytometry results showed that both cell types after exposure to 10Gy and harvested at 12 hr post-irradiation exhibited G2 arrest. G1 arrest was also observed in the wild-type but not in the knockout cells. For each cell line, microarray data revealed a small number of differentially expressed genes between irradiated and their control counterparts. However, more genes were differentially expressed between non-irradiated Ku80 knockout and wild-type cells and between irradiated ones. In our study, gene expression data appear to indicate that genes involved in nucleotide excision repair, homologous recombination repair and non-homologous end rejoining repair are preferably stimulated. In both cell lines, cyclin G, which is regulated by p53 protein post damage, has high gene expression level. These preliminary gene expression data suggest that further time-dependent study may reveal molecular pathways.
Частини книг з теми "KU70 gene"
1
Yin, Liu-hua, Lan Zhang, Ling Liu, Hongfei Zhang, Li Hou, and De-pei Wang. "Exploitation of a KU70-Deficient Mutant for Improving Gene Deletion Frequency in Aspergillus niger." In Lecture Notes in Electrical Engineering, 105–15. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/978-981-10-4801-2_11.
Повний текст джерела
2
Mak, Tak W., Josef Penninger, John Roder, Janet Rossant, and Mary Saunders. "Ku80." In The Gene Knockout FactsBook, 653–54. Elsevier, 1998. http://dx.doi.org/10.1016/b978-012466044-1/50365-3.
Повний текст джерелаТези доповідей конференцій з теми "KU70 gene"
1
De Figueiredo, Wenberger Lanza Daniel, Paula Taquita Serra, and Diego Monteiro De Carvalho. "UTILIZAÇÃO DO SISTEMA CRISPR-CAS9 PARA O TRATAMENTO DE CARCINOMA PAPILÍFERO DE TIREOIDE: REVISÃO DE LITERATURA." In I Congresso Brasileiro de Biotecnologia On-line. Revista Multidisciplinar de Educação e Meio Ambiente, 2021. http://dx.doi.org/10.51189/rema/1105.
Повний текст джерелаАнотація:
Introdução: O CRISPR/Cas9 é um sistema de tratamento para câncer baseado na edição do DNA que pode mudar os tratamentos para carcinoma papilífero de tireoide. Objetivo: Revisar na literatura a utilização do sistema CRISPR-CAS9 nos tratamentos para carcinoma papilífero de tireoide. Material e métodos: Realizou-se uma revisão de literatura combinando os seguintes descritores: “CRISPR-Associated Proteins e Thyroid Cancer, Papillary” nas plataformas PubMed, BVS e SciELO por artigos publicados há 5 anos completos e gratuitos. Por fim, incluiu-se 5 textos, 2 foram analisados por relacionarem-se ao tema do estudo. Resultados: As equipes de pesquisa do Reino Unido e da Grécia realizaram experimentação in vitro e in vivo de amostras retiradas de tecido vivo pós-cirúrgico com triagem por imuno-histoquímica de 170 amostras de tecido tireoidiano. O sistema de CRISPR/Cas9 possibilitou o knockdown de SLC35F2 em células cancerígenas que inibiu significativamente a proliferação, aboliu as habilidades de formação de colônias e atenuou a invasão e metástase de células cancerosas da tireoide. Dessa forma, viabilizou a suspeição do SLC35F2 como um importante preditor de metástases em linfonodos para pacientes com carcinoma de tireoide. Ademais, o knockdown por CRISPR/Cas9 de Ku80 reduziu significativamente a proliferação, invasão e formação de tumor em células tireoidianas. Teve efeitos no aumento significativo da taxa de apoptose, além de regular negativamente as moléculas relacionadas à via de sinalização de MAPK e proteínas associadas à proliferação e metástase das células. Por fim, demonstrou que o Ku80 está envolvido na patogênese do câncer de tireoide. Conclusão: Em suma, a técnica por CRISPR/Cas9 aplicada em cultura de células tumorais de tireoide demonstrou ser útil quanto ao silenciamento de genes envolvidos na metástase e proliferação. Assim, embora seja necessário melhor estudo do tema em humanos, supõe-se que a aplicação clínica futura em pacientes portadores da doença será possível.
Звіти організацій з теми "KU70 gene"
1
Weil, Clifford F., Anne B. Britt, and Avraham Levy. Nonhomologous DNA End-Joining in Plants: Genes and Mechanisms. United States Department of Agriculture, July 2001. http://dx.doi.org/10.32747/2001.7585194.bard.
Повний текст джерелаАнотація:
Repair of DNA breaks is an essential function in plant cells as well as a crucial step in addition of modified DNA to plant cells. In addition, our inability to introduce modified DNA to its appropriate locus in the plant genome remains an important hurdle in genetically engineering crop species.We have taken a combined forward and reverse genetics approach to examining DNA double strand break repair in plants, focusing primarily on nonhomologous DNA end-joining. The forward approach utilizes a gamma-plantlet assay (miniature plants that are metabolically active but do not undergo cell division, due to cell cycle arrest) and has resulted in identification of five Arabidopsis mutants, including a new one defective in the homolog of the yeast RAD10 gene. The reverse genetics approach has identified knockouts of the Arabidopsis homologs for Ku80, DNA ligase 4 and Rad54 (one gene in what proves to be a gene family involved in DNA repair as well as chromatin remodeling and gene silencing)). All these mutants have phenotypic defects in DNA repair but are otherwise healthy and fertile. Additional PCR based screens are in progress to find knockouts of Ku70, Rad50, and Mre11, among others. Two DNA end-joining assays have been developed to further our screens and our ability to test candidate genes. One of these involves recovering linearized plasmids that have been added to and then rejoined in plant cells; plasmids are either recovered directly or transformed into E. coli and recovered. The products recovered from various mutant lines are then compared. The other assay involves using plant transposon excision to create DNA breaks in yeast cells and then uses the yeast cell as a system to examine those genes involved in the repair and to screen plant genes that might be involved as well. This award supported three graduate students, one in Israel and two in the U.S., as well as a technician in the U.S., and is ultimately expected to result directly in five publications and one Masters thesis.
2
Tzfira, Tzvi, Michael Elbaum, and Sharon Wolf. DNA transfer by Agrobacterium: a cooperative interaction of ssDNA, virulence proteins, and plant host factors. United States Department of Agriculture, December 2005. http://dx.doi.org/10.32747/2005.7695881.bard.
Повний текст джерелаАнотація:
Agrobacteriumtumefaciensmediates genetic transformation of plants. The possibility of exchanging the natural genes for other DNA has led to Agrobacterium’s emergence as the primary vector for genetic modification of plants. The similarity among eukaryotic mechanisms of nuclear import also suggests use of its active elements as media for non-viral genetic therapy in animals. These considerations motivate the present study of the process that carries DNA of bacterial origin into the host nucleus. The infective pathway of Agrobacterium involves excision of a single-stranded DNA molecule (T-strand) from the bacterial tumor-inducing plasmid. This transferred DNA (T-DNA) travels to the host cell cytoplasm along with two virulence proteins, VirD2 and VirE2, through a specific bacteriumplant channel(s). Little is known about the precise structure and composition of the resulting complex within the host cell and even less is known about the mechanism of its nuclear import and integration into the host cell genome. In the present proposal we combined the expertise of the US and Israeli labs and revealed many of the biophysical and biological properties of the genetic transformation process, thus enhancing our understanding of the processes leading to nuclear import and integration of the Agrobacterium T-DNA. Specifically, we sought to: I. Elucidate the interaction of the T-strand with its chaperones. II. Analyzing the three-dimensional structure of the T-complex and its chaperones in vitro. III. Analyze kinetics of T-complex formation and T-complex nuclear import. During the past three years we accomplished our goals and made the following major discoveries: (1) Resolved the VirE2-ssDNA three-dimensional structure. (2) Characterized VirE2-ssDNA assembly and aggregation, along with regulation by VirE1. (3) Studied VirE2-ssDNA nuclear import by electron tomography. (4) Showed that T-DNA integrates via double-stranded (ds) intermediates. (5) Identified that Arabidopsis Ku80 interacts with dsT-DNA intermediates and is essential for T-DNA integration. (6) Found a role of targeted proteolysis in T-DNA uncoating. Our research provide significant physical, molecular, and structural insights into the Tcomplex structure and composition, the effect of host receptors on its nuclear import, the mechanism of T-DNA nuclear import, proteolysis and integration in host cells. Understanding the mechanical and molecular basis for T-DNA nuclear import and integration is an essential key for the development of new strategies for genetic transformation of recalcitrant plant species. Thus, the knowledge gained in this study can potentially be applied to enhance the transformation process by interfering with key steps of the transformation process (i.e. nuclear import, proteolysis and integration). Finally, in addition to the study of Agrobacterium-host interaction, our research also revealed some fundamental insights into basic cellular mechanisms of nuclear import, targeted proteolysis, protein-DNA interactions and DNA repair.