• Title/Summary/Keyword: Repair of Regulation

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Phosphorylation of p53 at threonine 155 is required for Jab1-mediated nuclear export of p53

  • Lee, Eun-Woo;Oh, Wonkyung;Song, Hosung Paul;Kim, Won Kon
    • BMB Reports
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    • v.50 no.7
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    • pp.373-378
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    • 2017
  • The Jun activation-domain binding protein 1 (Jab1) induces p53 nuclear export and cytoplasmic degradation, but the underlying mechanism is poorly understood. Here, we show that phosphorylation at the threonine 155 residue is essential for Jab1-mediated p53 nuclear export. Jab1 stimulated phosphorylation of p53 at T155 was inhibited by curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases. The T155E mutant, which mimics phosphorylated p53, exhibited spontaneous cytoplasmic localization in the absence of Jab1. This process was prevented by leptinomycin B (LMB), but not by curcumin. The substitution of threonine 155 for valine (T155V) abrogated Jab1-mediated p53 nuclear export, indicating that phosphorylation at this site is essential for Jab1-mediated regulation of p53. Although T155E can be localized in the cytoplasm in the absence of Mdm2, the translocation of T155E was significantly enhanced by ectopic Hdm2 expression. Our data suggests that Jab1-mediated phosphorylation of p53 at Thr155 residue mediates nuclear export of p53.

A DNA-Damage Response Gene Expression Analysis in MCF-7 followed by γ-Radiation (MCF-7 세포주의 γ선에 의한 DNA 손상 반응 유전자 발현 양상의 분석)

  • Park Ji-Yoon;Hwang Chang-Il;Park Woong-Yang;Kim Jin-Kyu;Chai Young Gyu
    • Korean Journal of Environmental Biology
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    • v.23 no.1
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    • pp.21-26
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    • 2005
  • Cell response to genotoxic agents is complex and involves the participation of different classes of genes including cell cycle control, DNA repair and apoptosis. In this report, we presented a approach to characterize the cellular functions associated with the altered transcript profiles of MCF-7 exposed to low-dose in vitro gamma-irradiation. We used the method of human 2.4 k cDNA microarrays containing apoptosis, cell cycle, chromatin, repair, stress and chromosome genes to analyze the differential gene expression characterization that were displayed by radiation-exposed cell, human breast carcinoma MCF-7 cell line, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. Among these genes, 66 were up-regulated and 49 were down-regulated. Specific genes were concomitantly induced in the results. Cyclin dependent kinase 4 (Cdk4) is induced for starting the cell cycle. This regulation is required for a DNA damage­induced G1 arrest. In addition to, an apoptotic pathways gene Bcl-w was concomitantly induced. Mismatch repair protein homologue-l (hMLH1), a necessary component of DNA mismatch protein repair (MMR), in G2-M cell cycle checkpoint arrest. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research.

The Effects of the Combined Biofeedback and Brief Emotion Regulation Nursing Intervention Based on the Gross Model for Sexually Abused Adolescents (성폭력 피해 청소년을 위한 바이오피드백 병행 Gross 모델기반 단기 정서조절 간호중재 효과)

  • Kim, Jieun;Park, Wanju
    • Journal of Korean Academy of Nursing
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    • v.52 no.6
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    • pp.608-623
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    • 2022
  • Purpose: This study aimed to evaluate the effects of a combined biofeedback and brief emotion regulation (C-BABER) program for sexually abused adolescents. Methods: This study employed a non-equivalent control group pretest-posttest design. The participants included 26 sexually abused adolescents from eight Sunflower Centers of South Korea-with 13 in the experimental group and 13 in the control group. The experimental group received four sessions of the individual C-BABER program, each lasting 60 minutes. Results: Compared with the control group, sexually abused adolescents in the experimental group exhibited significant score differences in traumatic symptoms, including depression (Z = - 2.24, p = .025), dissociation (Z = - 2.21, p = .027), anxiety (Z = - 2.02, p = .044), and posttraumatic stress (Z = - 2.01 p = .045); and impulsivity, including positive urgency (Z = - 3.35, p = .001) and negative urgency (Z = - 2.28, p = .023). Additionally, the experimental group exhibited significant score differences in meta-mood, including emotional attention (Z = - 2.45, p = .014), emotional clarity (Z = - 2.30, p = .021), and emotional repair (Z = - 2.28, p = .022); and emotional regulation modes, including emotional suppression (Z = - 2.65, p = .008) and cognitive reappraisal (Z = - 1.98, p = .047). Regarding bio-attention, significant changes were identified in the experimental group for the bio-attention rate and attention maintenance time in the posttest compared to the pretest (p = .001). Conclusion: The C-BABER program for sexually abused adolescents is effective in decreasing traumatic symptoms and impulsivity, and in improving meta-mood, emotional regulation mode, and bio-attention. Therefore, we recommend providing sexually abused adolescents the C-BABER program to help them regulate their emotions and effectively adapt to their lives.

Basic Properties of Polymer Cement Composites with Polymer Dispersions and Cement for Crack Repair (폴리머 디스퍼전과 시멘트로 만든 균열보수용 폴리머 시멘트 복합체의 기초적 성질)

  • Young-Kug Jo
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.27 no.5
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    • pp.97-104
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    • 2023
  • The aim of this study was to produce polymer cement composites (PCCs) composed of polymer dispersion and cement as crack repair materials for RC structures, and to investigate their fundamental properties. The test mixtures for the study were based on EVA and SAE polymer dispersions, and the water-cement ratio was determined while varying the polymer-cement ratio(P/C) in four different levels (20%, 60%, 80%, and 100%) to achieve the desired viscosity of PCCs considering their fillability as crack repair materials. Additionally, silica fume was incorporated into P/C 80% and 100% specimens to enhance their stiffness. The basic properties of PCCs as crack repair materials, such as viscosity, flowability, fillability, tensile strength, elongation, and modulus of elasticity, were examined. The results showed that P/C depending on the type of polymer significantly affected the viscosity and flowability, and appropriate w/c ratios were needed to achieve the desired viscosity for the mixture design with consideration of fillability as crack repair materials for RC structures. All designed mixtures in this study exhibited excellent fillability. The tensile strength and elongation of PCCs satisfied the KS regulation for cement- polymer modified waterproofing coatings. The incorporation of silica fume improved the tensile strength and modulus of elasticity of PCCs. Depending on the type of polymer, mixtures using SAE showed better fundamental properties as crack repair materials for RC structures compared to those using EVA. In conclusion, SAE-based P/C 80% or 100% with the addition of up to 30% silica fume can be recommended as suitable mixtures for crack repair of RC structures.

Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair

  • Yuna Kim;Baeki E. Kang;Karim Gariani;Joanna Gariani;Junguee Lee;Hyun-Jin Kim;Chang-Woo Lee;Kristina Schoonjans;Johan Auwerx;Dongryeol Ryu
    • BMB Reports
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    • v.57 no.2
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    • pp.98-103
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    • 2024
  • The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

The Regulation of LexA on UV-Induced SOS Response in Myxococcus xanthus Based on Transcriptome Analysis

  • Sheng, Duo-hong;Wang, Ye;Wu, Shu-ge;Duan, Rui-qin;Li, Yue-zhong
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.912-920
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    • 2021
  • SOS response is a conserved response to DNA damage in prokaryotes and is negatively regulated by LexA protein, which recognizes specifically an "SOS-box" motif present in the promoter region of SOS genes. Myxococcus xanthus DK1622 possesses a lexA gene, and while the deletion of lexA had no significant effect on either bacterial morphology, UV-C resistance, or sporulation, it did delay growth. UV-C radiation resulted in 651 upregulated genes in M. xanthus, including the typical SOS genes lexA, recA, uvrA, recN and so on, mostly enriched in the pathways of DNA replication and repair, secondary metabolism, and signal transduction. The UV-irradiated lexA mutant also showed the induced expression of SOS genes and these SOS genes enriched into a similar pathway profile to that of wild-type strain. Without irradiation treatment, the absence of LexA enhanced the expression of 122 genes that were not enriched in any pathway. Further analysis of the promoter sequence revealed that in the 122 genes, only the promoters of recA2, lexA and an operon composed of three genes (pafB, pafC and cyaA) had SOS box sequence to which the LexA protein is bound directly. These results update our current understanding of SOS response in M. xanthus and show that UV induces more genes involved in secondary metabolism and signal transduction in addition to DNA replication and repair; and while the canonical LexA-dependent regulation on SOS response has shrunk, only 5 SOS genes are directly repressed by LexA.

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

  • Sarkar, Shreya;Maiti, Guru Prasad;Jha, Jayesh;Biswas, Jaydip;Roy, Anup;Roychoudhury, Susanta;Sharp, Tyson;Panda, Chinmay Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6419-6425
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    • 2013
  • Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

A Study on Ubiquitous Road for Prevention of the Overweight Vehicles (과적차량 방지를 위한 유비쿼터스도로에 관한 연구)

  • Jo, Byung-Wan;Yoon, Kwang-Won;Park, Jung-Hoon;Kim, Heoun
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.21 no.3
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    • pp.225-232
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    • 2008
  • Overload vehicles operate damage to road, bridge, and then increasing in maintenance and repair cost because structures are reduced durability. The existing regulation systems have many problems and need coping measure. Therefore, this paper organized Ubiquitous sensor network system for development of intelligent auto overload vehicle regulation system about high speed vehicles, also axial load WIM sensor was selected by indoor experiment through wireless protocol. And we examined possibility U-load auto overload vehicle regulation system through experiment of the transmission and reception distance. If this system will apply to road and bridge, might be effective for economy and convenience through establishment of U-IT system. And high speed vehicle that was amalgamate IT technology and existing overload regulation problems, also tested wireless sensor for USN organization. This experiment aim to organize system interface for user through perfection man-less, wireless system of Internal/External Network from high speed WIN sensor with USN organization. Accordingly, it is necessary experimentation through Test Bed for constitution External network and application of actually regulations using WCDMA/HSDPA.

Molecular Cloning and Characterization of DNA Repair Related Gene in Yeast

  • Kang, Seon-Ah;Park, In-Soon
    • Journal of Life Science
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    • v.10 no.1
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    • pp.40-44
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    • 2000
  • The SNF2/SW ATPase/helicase family comprises proteins form a variety of species with in vivo functions, such as transcriptional regulation, maintenance of chromosome stability during mitosis, and various types of DNA repair. Here, we reported the characterization of h게2+gene which was iolated by PCR amplification using the conserved domain of SNF2 motifs. Sequence analysis of PCR product showed striking evolutionary conservation among the SNF2 family of proteins. Two transcripts of 6.7 and 3.4 Lb were detected by Northern blot analysis. furthermore, the intensities of these two bands were increased by ultraviolet(UV) irradiation. These results indicate that the hrp2+ is a novel member of the SNF2 family of proteins and is one of the UV-inducible genes in S. pombe. To determine the level of transcripts of hrp2+ gene during cellular growth, Northern blot analysis were performed. This result indicates that the level of hrp2+transcript reached its maximum before cells entered the exponential growth phase. This suggests that hrp2+ gene is experssed mainly at the early stage of cell growth.

The Role of Gene-environment Interaction in Environmental Carcinogenesis (환경성 발암 기전에서 유전자-환경 상호작용의 역할)

  • Han, So-Hee;Lee, Kyoung-Mu
    • Journal of Environmental Health Sciences
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    • v.36 no.1
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    • pp.1-13
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    • 2010
  • Evidences supporting gene-environment interaction are accumulating in terms of environmental exposure including lifestyle factors and related genetic variants. One form of defense mechanism against cancer development involves a series of genes whose role is to metabolize (activation/detoxification) and excrete potentially toxic compounds and to repair subtle mistakes in DNA. The purpose of this article is to provide a brief review of the notion of gene-environment interaction, environmental/occupational carcinogens and related cancers, and previous studies of gene-environment interaction on cancers caused by exposure to carcinogenesis. With a number of studies on the interaction between lifestyle factors (e.g., smoking and diet) and genetic polymorphisms in genes involved in xenobiotic metabolism and DNA repair excluded, only several studies have been conducted on the interactive effects between polymorphisms of CYPs, GSTs, ERCCs, XRCCs and environmental/occupational carcinogens such as vinyl chloride, benzo[a]pyrene, and chloroform on carcinogenesis or genotoxicity. Future studies may need to be conducted with sufficient number of subjects and based on occupational cohorts to provide useful information in terms of advanced risk assessment and regulation of exposure level.