• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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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)

• Radiation Oncology Journal
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• 제13권2호
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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.

• Molecules and Cells
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• 제38권1호
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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.

• 환경생물
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• 제23권1호
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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.

• 환경생물
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• 제29권1호
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• pp.68-73
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• 2011

E. fetida를 방사선과 수은에 각각 노출시킨 후, 체강세포를 추출하고 단세포 겔 전기영동 기법을 이용하여 DNA의 손상정도와 시간의 경과에 따른 수복 양상을 평가해 보았다. 그 결과, 방사선 조사 후의 시간이 경과할수록 대체로 DNA 손상정도가 감소했으며, 12시간 내에 모든 실험군의 DNA가 완전히 수복되었다. 정확한 수복 완료 시간을 알아보기 위해 OTM 값을 대조군과 비교해 보면 2.5와 5Gy는 방사선 조사 후 약 2시간, 10과 20 Gy는 약 3시간, 50 Gy는 약 12시간이 지나자 DNA가 완전히 회복된다고 판단할 수 있었다. 또한 지렁이를 80과 160 mg $kg^{-1}$ 농도의 염화수은(II)에 48시간 동안 노출시킨 후, 수은에 오염되지 않은 깨끗한 배양토에서 72시간을 다시 배양했을 때 손상된 DNA가 완전히 수복되었다. 본 연구 결과는 산화적 스트레스 인자에 대한 생물의 민감도를 측정하는 자료로 제시될 수 있으며, 향후 다양한 생물을 대상으로 실험을 진행한다면 동일한 유전독성 물질에 대한 생물종 간의 감수성을 비교 분석할수 있을 것이다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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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)

• 한국환경성돌연변이발암원학회지
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• 제9권2호
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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.

• 한국환경성돌연변이발암원학회지
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• 제19권1호
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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.

• Archives of Pharmacal Research
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• 제18권4호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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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.