• Title/Summary/Keyword: DNA-repair

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RECOMMENDED DIETARY ALLOWANCES FOR GENOMIC STABILITY

  • Fenech, Michael
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.9-9
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    • 2001
  • Several micronutrients (vitamins and minerals) are required as co-factors in DNA synthesis, DNA repair, DNA methylation and apoptosis. Some notable examples include (a) folic acid and vitamin B12 required for maintenance methylation of DNA and the synthesis of dTTP from dUTP, thus prevent the misincorporation of uracil into DNA, a highly mutagenic and chromosome-breaking event, (b) niacin, is essential in the form of the coenzymes NAD and NADP which act as a substrate for polyADPribose polymerase (PARP), an enzyme thought to facilitate efficient DNA repair and telomere length regulation and (c) zinc, apart from its antioxidant role as a co-factor in Cu/Zn SOD, it is required in its stabilizing role of the DNA-binding domain of p53 (residues 102-292) and thus is essential for apoptotic response to DNA damage. (omitted)

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The Effects of Alkaloid Fraction of Korean Ginseng on the Radiation-Induced DNA Strand Breaks (방사선 조사에 의한 DNA Double Strand Breaks의 생성 및 회복에 미치는 인삼 알칼로이드 분획의 효과)

  • Cho Chul Koo;Kim Tae Hwan;Yoo Seong Yul;Koh Kyoung Hwan;Kim Mi Sook;Kim Jeong Hee;Kim Seong Ho;Yoon Hyung Keun;Ji Young Hoon
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.113-120
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    • 1995
  • Purpose : To investigate the effect of alkaloid fraction from Korean ginseng on radiation-induced DNA double strand breaks (dsb) formation and repair in murine lymphocytes Materials and Methods : We used the neutral filter elution technique to assay $^{60}Co\;{\gamma}$ ray-induced DNA double strand breaks formation and repair in C57BL/6 mouse spleen lymphocytes for evaluating the dose-response relationship in the presence of alkaloid fraction as a radioprotective agent. The lymphocytes were stimulated with Phytohemagglutinin (PHA, 2 u g/ml) to label $^3[H]-thymidine.$ Isotope-labelled lymphocytes in suspension were exposed to 100 Gy at $0^{\cdot}C$ in the alkaloid fraction-treated group and elution procedure was performed at PH 9.6. The extents of formation of radiation-induced DNA double strand breaks and repair were compared respectively via strand scission factor (SSF) and relative strand scission factor (RSSF). Results: Alkaloid fraction reduced the formation of double strand breaks with dose modification factor of 2 15, compared to control group Rejoining of DNA dsb appeared to take place via two components. The first fast component was completed within 20.4 minutes, but the second slow component was not completed until 220.2 minutes after irradiation. About $30\%$ of dsb formed by irradiation was ultimately unrejoined despite the administration of alkaloid fraction. The administration of alkaloid fraction had a great effect on the second slow component of repair; the half-time of fast component repair was not changed, but that of slow component was 621.8 minutes. Conclusion: Neutral filter elution assay Proved to be a very effective method to quantitate the extents of DNA dsb formation and its repair. By using this technique, we were able to evaluate the efficiency of alkaloid fraction from Korean ginseng as a valuable radioprotector. Alkaloid fraction can be used prophylactically to prevent or ameliorate the severe radiation damages in workers and neighbors around the atomic power plants. For more refined study, however, more advanced purification of alkaloid fraction wil be needed in the near future.

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Stimulation of Oligonucleotide-Directed Gene Correction by Redβ Expression and MSH2 Depletion in Human HT1080 Cells

  • Xu, Ke;Stewart, A. Francis;Porter, Andrew C.G.
    • Molecules and Cells
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    • v.38 no.1
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    • pp.33-39
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    • 2015
  • The correction of disease-causing mutations by single-strand oligonucleotide-templated DNA repair (ssOR) is an attractive approach to gene therapy, but major improvements in ssOR efficiency and consistency are needed. The mechanism of ssOR is poorly understood but may involve annealing of oligonucleotides to transiently exposed single-stranded regions in the target duplex. In bacteria and yeast it has been shown that ssOR is promoted by expression of $Red{\beta}$, a single-strand DNA annealing protein from bacteriophage lambda. Here we show that $Red{\beta}$ expression is well tolerated in a human cell line where it consistently promotes ssOR. By use of short interfering RNA, we also show that ssOR is stimulated by the transient depletion of the endogenous DNA mismatch repair protein MSH2. Furthermore, we find that the effects of $Red{\beta}$ expression and MSH2 depletion on ssOR can be combined with a degree of cooperativity. These results suggest that oligonucleotide annealing and mismatch recognition are distinct but interdependent events in ssOR that can be usefully modulated in gene correction strategies.

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.

Evaluation of DNA Damage and Repair Kinetics in the Earthworm (Eisenia fetida) Exposed to Radiation and Mercury (방사선과 수은에 의해 유도된 Eisenia fetida 체강세포의 DNA 손상 및 수복 평가)

  • Ryu, Tae-Ho;Nili, Mohammad;An, Kwang-Guk;Kim, Jin-Kyu
    • Korean Journal of Environmental Biology
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    • v.29 no.1
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    • pp.68-73
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    • 2011
  • The single cell gel electrophoresis (SCGE) assay is a microelectrophoretic technique for assessments of DNA damage at the level of the individual eukaryotic cell. The SCGE assay, due to its simplicity, sensitivity and need of a few cells, has advantages compared to other genomic damage assays such as sister chromatid exchange, chromosomal aberration and micronucleus test. In this study, investigated were the levels of DNA damage and the repair kinetics in the coelomocytes of Eisenia fetida treated with HgCl2 and ionizing radiation by means of the SCGE assay. For detecting DNA damage and repair in coelomocytes, earthworms (E. fetida) were irradiated with six doses of ${\gamma}$-rays (0, 2.5, 5, 10, 20 and 50 Gy) and in vivo exposed to mercuric chloride at 0, 80 and 160 mg $kg^{-1}$ for 48 hours. Then the Olive tail moments were measured during 0~12 hours after irradiation and 0~72 hours after Hg treatment. The results showed that the more the oxidative stress was induced by mercury and radiation, the longer the repair time was required. Also, the results suggest that the SCGE assay may be used as an important tool for comparison of the sensitivity of different species to oxidative stresses.

NMR and Molecular Modeling Studies on the Structures of AA Mismatched DNA Oligomers

  • Lee, Chulhyun;Chaejoon Cheong;Lee, Jo-Woong
    • Proceedings of the Korean Biophysical Society Conference
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    • 1998.06a
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    • pp.21-21
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    • 1998
  • Since the repair efficiency of non-Watson-Crick base pairs in DNA is affected by the mismatched base-pairs and their neighbor sequences, the structural studies are necessary for the elucidation of the repair efficiency. NMR and molecular modeling studies on the DNA duplexes including AA mismatches were performed.(omitted)

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Pseudomonas 균주에 있어서 R2 Plasmid 획득에 의한 Gamma-ray 내성증강

  • 조봉금
    • Environmental Mutagens and Carcinogens
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    • v.9 no.2
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    • pp.111-121
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    • 1989
  • Ps. aeruginosa 의 DNA repair 기구 결손변이주인 rec-, Hcr- 그리고 R931 plasmid 를 가진 R2 (Carbenicillin, Kanamycin, Streptomycin) plasmid transconjugants 가 R2 Plasmid 획득에 의해서 Gamma선 및 돌연변이제 (4NQO, NTG)에 대해서도 내성을 증강시키는지를 검토함으로써 방사선에 대한 내성화 기구를 해명하고자 했다. 그리고, DNA repair 기구에 작용하는 DNA polymerase I 생산에 관여하는 유전자가 R2 plasmid에 code 되어 있는지를 검토하여 다음과 같은 결과를 얻었다. 1) Ps. aeruginosa PAO균주의 R2 plasmid transconjugants는 R2 plasmid 획득에 의해 자외선, Gamma선 및 돌연변이제에 대한 내성을 부여받았으나 transconjugant 균주에 따라 다른 종류의 내성결과를 얻어졌다.

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Isolation and Characterization of New Family Genes of DNA Damage in Fission Yeast

  • Choi, In-Soon
    • Environmental Mutagens and Carcinogens
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    • v.19 no.1
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    • pp.28-33
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    • 1999
  • The SNF2 family includes proteins from a variety of species with roles I cellular processes such as transcriptional regulation, recombination and various types of DNA repair. Several proteins with unknown function are also included in this family. Here, we report the cloning and characterization of hrp 2+ gene (helicase related gene from S. pombe) which was isolated by PCR amplication using the conserved domain of SNF2 motifs within the ERCC6 gene which encodes a protein involved in DNA excision repair. The hrp2+ gene was isolated by screening with yeast S. pombe genomic library. The isolated cloned contained 6.5 kb insert DNA. Southern blot analysis confirmed that S. pombe chromosome contains the same DNA as hrp2+ gene and this gene exists as a single copy in S. pombe genome. The 4.7 kb transcript of mRNA was identified by Northern blot. To examined the transcriptional regulation of hrp2+ gene, DNA damaging agents were treated. These results indicated that the hrp2+ gene may not be directly involved in DNA replication, but may be involved in damage response pathway.

Characterization of Several Transformation-deficient Mutants of Streptococcus pneumoniae in DNA Damage

  • Kim, Seung-Whan;Rhee, Dong-Kwon
    • Archives of Pharmacal Research
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    • v.18 no.4
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    • pp.243-248
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    • 1995
  • Seventeen transformation-deficient mutants of streptococcus pneumoniae, which are defective in competence induction (com), DNA uptake(ent) of recombination(rec), were investigated to determine sensitivity to ethylmethane sulfonate(EMS), methylmethane sulfonate(MMS), UV and mitomycin C. In ethylmethane sulfonate assay, the viability of most $com^-, \; rec^-\; and ent^-$ mutants was decreased about 2-10 times and the viability of ent-9 and ent-13 mutant was decreased about 33 and 25 times, respectively. On the other hand only half of the transformation-deficient mutants tested was sensitive to methylmethane sulfonate about 2 times and ent-12 mutant was sensitive to 2.0% MMS about 8 times. After UV and mitomycin C treatment, most of the mutants are not sensitive to UV and mitomycin C, although the viability of some transformation-deficient mutants was decreased slightly. Especially none of the com mutants were sensitive to DNA damage suggesting that competence is not involved in DNA repair. Also DNA uptake and recombination gane might be related to DNA repair function.

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DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

  • Guo, Cheng-Xian;Yang, Guo-Ping;Pei, Qi;Yin, Ji-Ye;Tan, Hong-Yi;Yuan, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.713-718
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    • 2015
  • Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.