• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권1호
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• pp.1-6
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• 2009

DNA double-strand breaks (DSBs) occur commonly in the all living and in cycling cells. They constitute one of the most severe form of DNA damage, because they affect both strand of DNA. DSBs result in cell death or a genetic alterations including deletion, loss of heterozygosity, translocation, and chromosome loss. DSBs arise from endogenous sources like metabolic products and reactive oxygen, and also exogenous factors like ionizing radiation. Defective DNA DSBs can lead to toxicity and large scale sequence rearrangement that can cause cancer and promote premature aging. There are two major pathways for their repair: homologous recombination(HR) and non-homologous end-joining(NHEJ). The HR pathway is a known "error-free" repair mechanism, in which a homologous sister chromatid serves as a template. NHEJ, on the other hand, is a "error-prone" pathway, in which the two termini of the broken DNA molecule are used to form compatible ends that are directly ligated. This review aims to provide a fundamental understanding of how HR and NHEJ pathways operate, cause genome instability, and what kind of genes during the pathways are associated with head and neck cancer.

• BMB Reports
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• 제52권10호
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• pp.607-612
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• 2019

During meiosis, programmed double-strand breaks (DSBs) are repaired via recombination pathways that are required for faithful chromosomal segregation and genetic diversity. In meiotic progression, the non-homologous end joining (NHEJ) pathway is suppressed and instead meiotic recombination initiated by nucleolytic resection of DSB ends is the major pathway employed. This requires diverse recombinase proteins and regulatory factors involved in the formation of crossovers (COs) and non-crossovers (NCOs). In mitosis, spontaneous DSBs occurring at the G1 phase are predominantly repaired via NHEJ, mediating the joining of DNA ends. The Ku complex binds to these DSB ends, inhibiting additional DSB resection and mediating end joining with Dnl4, Lif1, and Nej1, which join the Ku complex and DSB ends. Here, we report the role of the Ku complex in DSB repair using a physical analysis of recombination in Saccharomyces cerevisiae during meiosis. We found that the Ku complex is not essential for meiotic progression, DSB formation, joint molecule formation, or CO/NCO formation during normal meiosis. Surprisingly, in the absence of the Ku complex and functional Mre11-Rad50-Xrs2 (MRX) complex, a large portion of meiotic DSBs was repaired via the recombination pathway to form COs and NCOs. Our data suggested that Ku complex prevents meiotic recombination in the elimination of MRX activity.

• Korean Journal of Radiology
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• 제21권8호
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• pp.967-977
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• 2020

Objective: To evaluate the effects of tube voltage on image quality in coronary CT angiography (CCTA), the estimated radiation dose, and DNA double-strand breaks (DSBs) in peripheral blood lymphocytes to optimize the use of CCTA in the era of low radiation doses. Materials and Methods: This study included 240 patients who were divided into 2 groups according to the DNA DSB analysis methods, i.e., immunofluorescence microscopy and flow cytometry. Each group was subdivided into 4 subgroups: those receiving CCTA only with different tube voltages of 120, 100, 80, or 70 kVp. Objective and subjective image quality was evaluated by analysis of variance. Radiation dosages were also recorded and compared. Results: There was no significant difference in demographic characteristics between the 2 groups and 4 subgroups in each group (all p > 0.05). As tube voltage decreased, both image quality and radiation dose decreased gradually and significantly. After CCTA, γ-H2AX foci and mean fluorescence intensity in the 120-, 100-, 80-, and 70-kVp groups increased by 0.14, 0.09, 0.07, and 0.06 foci per cell and 21.26, 9.13, 8.10, and 7.13 (all p < 0.05), respectively. The increase in the DNA DSB level in the 120-kVp group was higher than those in the other 3 groups (all p < 0.05), while there was no significant difference in the DSBs levels among these latter groups (all p > 0.05). Conclusion: The 100-kVp tube voltage may be optimal for CCTA when weighing DNA DSBs against the estimated radiation dose and image quality, with further reductions in tube voltage being unnecessary for CCTA.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.4879-4881
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• 2012

Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. The EGFR modulates DNA repair after radiation-induced damage through an association with the catalytic subunit of DNA protein kinase. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation, and non-homologous end joining is the predominant pathway for repair of radiation-induced DSBs. Some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer. These pathways also invoke the cell survival mechanisms that lead to resistance to radiation. The molecular connection between the EGFR and its control over DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this mini-review was not only to highlight the relation of the EGFR signal as a regulatory mechanism to DNA repair and radiation resistance, but also to provide clues to improving existing radiation resistance through novel therapies based on the above-mentioned mechanism.

• 방사선산업학회지
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• 제10권4호
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• pp.243-248
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• 2016

Argonaute 2 (AtAGO2) is a well characterized effector protein in Arabidopsis for its functionalities associated with DNA double-strand break (DSB)-induced small RNAs (diRNAs) and for its inducible expression upon ${\gamma}$-irradiation. However, its transcriptional regulation depending on the recovery time after the irradiation and on the specific response to DSBs has been poorly understood. We analyzed the 1,313 bp promoter sequence of the AtAGO2 gene ($1.3kb_{pro}$) to characterize the transcriptional regulation of AtAGO2 at various recovery times after ${\gamma}$-irradiation. A stable transformant harboring $1.3kb_{pro}$ fused with GUS gene showed that the AtAGO2 is highly expressed in response to ${\gamma}$-irradiation, after which the expression of the gene is gradually decreased until 5 days of DNA damage recovery. We also confirm that the AtAGO2 expression patterns are similar to that of ${\gamma}$-irradiation after the treatments of radiomimetic genotoxins (bleomycin and zeocin). However, methyl methanesulfonate and mitomycin C, which are associated with the inhibition of DNA replication, do not induce the expression of the AtAGO2, suggesting that the expression of the AtAGO2 is closely related with DNA DSBs rather than DNA replication.

• 미생물학회지
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• 제49권1호
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• pp.1-7
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• 2013

유전자 재조합체는 상동염색체간의 예정된 DNA 가닥 전이와 교환이 이루어지는 상동염색체 재조합 과정에 의하여 생성된다. 이 재조합 경로는 DNA 이중 가닥 절단(double-strand breaks, DSBs)에 의해서 개시되며, 전이 과정의 중간단계에서 DNA의 구조적 변이 중간체인 단일 가닥 침투(single-end invasions, SEIs)와 이중 홀리데이 접합(double-Holliday junctions, dHJs)이 형성되어 교차성(crossover, CO) 혹은 비교차성(non-crossover, NCO) 결과물이 만들어진다. 본 연구는 이중 가닥 절단, 단일 가닥 침투, 이중 홀리데이 접합과 같은 재조합 중간체와 재조합 결과물의 구조분석에 초점을 두고, 이를 출아효모에서 인위적으로 이중 가닥 절단을 발생시킬 수 있는 HIS4LEU2 "hot spot" 을 이용한 물리적 분석방법으로 감수분열 재조합 중간체를 규명하였다. 물리적 분석을 위하여 동조화 된 세포에 감수분열을 유도한 후 hot spot 자리를 인식하는 제한효소를 처리하면, 재조합 중간체를 형성하고 있는 DNA 단편들을 Southern 분석법을 통해 탐지 및 정량 할 수 있다. 본 연구는 이 시스템으로 감수분열에서 이중가닥 절단으로부터 기인하는 단일 가닥 침투, 이중 홀리데이 접합 그리고 교차성/비교차성 재조합체로 전이되는 DNA의 구조 다형을 분석할 수 있음을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3301-3306
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• 2015

Nucleolin (C23) is an important anti-apoptotic protein that is ubiquitously expressed in exponentially growing eukaryotic cells. In order to understand the impact of C23 in radiation therapy, we attempted to investigate the relationship of C23 expression with the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. We investigated the role of C23 in activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a critical protein for DNA double-strand breaks (DSBs) repair. As a result, we found that the expression of C23 was negatively correlated with the radiosensitivity of NSCLC cell lines. In vitro clonogenic survival assays revealed that C23 knockdown increased the radiosensitivity of a human lung adenocarcinoma cell line, potentially through the promotion of radiation-induced apoptosis and adjusting the cell cycle to a more radiosensitive stage. Immunofluorescence data revealed an increasing quantity of ${gamma}$-H2AX foci and decreasing radiation-induced DNA damage repair following knockdown of C23. To further clarify the mechanism of C23 in DNA DSBs repair, we detected the expression of DNA-PKcs and C23 proteins in NSCLC cell lines. C23 might participate in DNA DSBs repair for the reason that the expression of DNA-PKcs decreased at 30, 60, 120 and 360 minutes after irradiation in C23 knockdown cells. Especially, the activity of DNA-PKcs phosphorylation sites at the S2056 and T2609 was significantly suppressed. Therefore we concluded that C23 knockdown can inhibit DNA-PKcs phosphorylation activity at the S2056 and T2609 sites, thus reducing the radiation damage repair and increasing the radiosensitivity of NSCLC cells. Taken together, the inhibition of C23 expression was shown to increase the radiosensitivity of NSCLC cells, as implied by the relevance to the notably decreased DNA-PKcs phosphorylation activity at the S2056 and T2609 clusters. Further research on targeted C23 treatment may promote effectiveness of radiotherapy and provide new targets for NSCLC patients.

• 대한치과보존학회:학술대회논문집
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• 대한치과보존학회 2008년도 Spring Scientific Meeting(the 129th) of Korean Academy if Conservative Dentistry
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• pp.213-223
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• 2008

광물리학적 특성 분석을 위해 Apollo 95E (DMT Systems, Orange, CA : PAC 광중합기), Elipar Freelight 2 (3M ESPE, MN, USA; LED 광중합기) 그리고 VIP Junior (Bisco, Schaumberg, IL, USA : QTH 광중합기), 3종의 광중합기의 총광강도(Total intensity)와 spectral distribution을 측정하였고 특정 파장에 해당되는 광강도(Energy density)를 분석하였다. 상아질 전단접착강도의 측정을 위해 Scotchbond Multipurpose (3M ESPE), Single bond (3M ESPE) 그리고 Clearfil SE bond (Kuraray)가 사용되었다. Plasma Arc Curing light (Apollo 95E) 광중합기는 여러개의 최대정점을 가지며 넓은 spectral distribution과 $2307mW/cm^2$의 높은 광강도를 나타내었고, VIP Junior 광중합기는 490 nm에서 최대정점을 갖는 넓은 spectral distribution을 나타내었고, Elipar Freeelight 2 광중합기는 462 nm의 최대정점 주위로 좁은 spectral distribution을 보였다. Two-Way ANOVA와 Bonferroni's multiple comparison test를 이용하여 상아질 전단접착강도를 분석한 결과, PAC 광중합기와 LED 광중합기 간에 유의성 있는 차이를 보이지 않았으며 (P > 0.05), 상아질 접착제와 광중합기의 교호관계에도 유의성이 없었다. 그러나 상아질 접착제는 상호간에 유의성 있는 차이를 보였다 (P < 0.00).

• Restorative Dentistry and Endodontics
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• 제33권3호
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• pp.213-223
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• 2008

광물리학적 특성 분석을 위해 Apollo 95E (DMT Systems, Orange, CA; PAC 광중합기), Elipar Freelight 2 (3M ESPE, MN, USA; LED 광중합기) 그리고 VIP Junior (Bisco, Schaumberg, IL, USA; QTH 광중합기), 3종의 광중합기의 총광강도(Total intensity)와 spectral distribution을 측정하였고 특정 파장에 해당되는 광강도 (Energy density)를 분석하였다. 상아질 전단접착강도의 측정을 위해 Scotchbond Multipurpose (3M ESPE), Single bond (3M ESPE) 그리고 Clearfil SE bond (Kuraray)가 사용되었다. Plasma Arc Curing light (Apollo 95E) 광중합기는 여러개의 최대정점을 가지며 넓은 spectral distribution과 $2307mw/cm^2$의 높은 광강도를 나타내었고, VIP Junior 광중합기는 490nm에서 최대정점을 갖는 넓은 spectral distribution을 나타내었고, Elipar Freeelight 2 광중합기는 462 nm의 최대정점 주위로 좁은 spectral distribution을 보였다. Two-Way ANOVA와 Bonferroni's multiple comparison test를 이용하여 상아질 전단접착강도를 분석한 결과, PAC 광중합기와 LED 광중합기 간에 유의성 있는 차이를 보이지 않았으며 (P > 0.05), 상아질 접착제와 광중합기의 교호관계에도 유의성이 없었다. 그러나 상아질 접착제는 상호간에 유의성 있는 차이를 보였다 (P < 0.001).

• Bulletin of the Korean Chemical Society
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• 제23권2호
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• pp.330-336
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• 2002

A quantum-chemical investigation on the conformations and electronic properties of bis[2-{2-methoxy-4,6-di(t-butyl)phenyl}ethenyl]benzenes (MBPBs) as building block for ${\pi}$-conjugate polymer are performed in order to display the effects of t-butyl and methoxy group substitution and of kink(ortho and meta) linkage. The conjugation length of the polymers can be controlled by substituents and kink linkages of backbone. Structures for the molecules, o-, m-, and p-MBPBs as well as unsubstituted o-, m-, and p-DSBs were fully optimized by using semiempirical AM1, PM3 methods, and ab initio HF method with 3-21G(d) basis set. The potential energy curves with respect to the change of single torsion angle are obtained by using semiempirical methods and ab initio HF/3-21G(d) basis set. The curves are similar shape in the molecules with respect to the position of vinylene groups. It is shown that the conformations of the molecules are compromised between the steric repulsion interaction and the degree of the conjugation. Electronic properties of the molecules were obtained by applying the optimized structures and geometries to the ZINDO/S method. ZINDO/S analysis performed on the geometries obtained by AM1 method and HF/3-21G(d) level is reported. The absorption wavelength on the geometries obtained by AM1 method is much longer than that by HF/3-21G(d) level. The absorption wavelength of MBPBs are red shifted with comparison to that of corresponding DSBs in the same torsion angle because of electron donating substituents. The absorption wavelength of isomers with kink(orth and meta) linkage is shorter than that of para linkage.