• Journal of Microbiology
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• 제41권2호
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• pp.115-120
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• 2003

Mex67p/Tap are evolutionally conserved mRNA export factors. To identify mutations in genes that are functionally linked to mex67 with respect to mRNA export, we used a synthetic lethal genetic screen in Schizosaccharomyces pombe. Three synthetic lethal mutants were isolated and mutations in these mutants defined separate complementation groups. These mutants exhibited the accumulation of poly A$\^$+/ RNA in the nucleus, with a decrease in the cytoplasm under synthetically lethal conditions, suggesting that the mutations cause an mRNA nuclear export defect. In addition, the S. pombe genes that were found to be involved in mRNA export did not suppress the synthetic lethality of these mutants. These results indicate that the isolated mutants contain mutations in new genes, which are involved in mRNA export from the nucleus.

• Journal of Microbiology
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• 제42권1호
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• pp.32-36
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• 2004

We have previously isolated three synthetic lethal mutants from Schizosaccharomyces pombe in order to identify mutations in the genes that are functionally linked to spmex67 with respect to mRNA export. A novel rsm1 gene was isolated by complementation of the growth defect in one of the synthetic lethal mutants, SLMex1. The rsml gene contains no introns and encodes a 296 amino-add-long protein with the RING finger domain, a C3HC4 in the N-terminal half. The Δrsm1 null mutant is viable, but it showed a slight poly(A)$\^$＋/ RNA accumulation in the nucleus. Also, the combination of Δrsm1 and Δspmex67 mutations confers synthetic lethality that is accompanied by the severe poly(A)$\^$＋/ RNA export defect. These results suggest that rsm1 is involved in mRNA export from the nucleus.

• 미생물학회지
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• 제42권2호
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• pp.149-152
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• 2006

분열효모인 Schizosaccharomyces pombe에서 mRNA의 핵에서 세포질로의 이동에 관여할 것으로 여겨지는 spThp1 유전자의 결실돌연변이주(deletion mutant)를 제조하여 그 특성을 조사하였다. 이배체(diploid) 균주의 한 spThp1 유전자를 결실시킨 후 4분체분석(tetrad analysis)을 수행한 결과, 이 유전자는 생장에 필수적이지 않았다. 또한 결실돌연변이주는 mRNA 수송도 큰 결함을 보이지 않았다. 하지만 spThp1 는 mRNA의 운반체를 암호화하고 있는 spMex67와 합성치사(synthetic lethality)를 보였다. 이 결과는 분열효모의 spThpl도 mRNA의 핵에서 세포질로의 이동에 역할을 하고 있음을 암시한다.

• Journal of Microbiology
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• 제45권4호
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• pp.344-349
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• 2007

We have isolated previously three synthetic lethal mutants in Schizosaccharomyces pombe, which genetically interact with mex67, in order to identify the genes involved in mRNA export. A novel nup97 gene was isolated by complementation of the growth defect in one of the synthetic lethal mutants, SLMex3. The nup97 gene contains one intron and encodes an 851 amino-acid protein that is similar to nucleoporins, Nppl06p in S. pombe and Nic96p in Saccharomyces cerevisiae. The nup97 gene is essential for vegetative growth, and nup97 null mutant harboring pREP41X-Nup97 showed $poly(A)^+$ RNA export defect when expression of nup97 is repressed in the presence of thiamine. These results suggest that nup97 is involved in mRNA export from the nucleus to cytoplasm.

• Journal of Microbiology and Biotechnology
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• 제21권7호
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• pp.719-727
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• 2011

Botulism is a neuroparalytic disease caused by Clostridium botulinum, which produces seven (A-G) antigenically diverse neurotoxins (BoNTs). BoNTs are the most poisonous substances known to humans, with a median lethal dose ($LD_{50}$) of approximately 1 ng/kg of body weight. Owing to their extreme potency and lethality, they have the potential to be used as a bioterrorism agent. The mouse bioassay is the gold standard for the detection of botulinum neurotoxins; however, it requires at least 3-4 days for completion. Attempts have been made to develop an ELISA-based detection system, which is potentially an easier and more rapid method of botulinum neurotoxin detection. The present study was designed using a synthetic gene approach. The synthetic gene encoding the catalytic domain of BoNT serotype B from amino acids 1-450 was constructed with PCR overlapping primers (BoNT/B LC), cloned in a pQE30 UA vector, and expressed in an E. coli M15 host system. Recombinant protein production was optimized at 0.5 mM IPTG final concentration, 4 h post induction, resulting in a maximum yield of recombinant proteins. The immunogenic nature of the recombinant BoNT/B LC protein was evaluated by ELISA. Antibodies were raised in BALB/c mice using various adjuvants. A significant rise in antibody titer (p<0.05) was observed in the Alum group, followed by the Titermax Classic group, Freund's adjuvant, and the Titermax Gold group. These developed high-titer antibodies may prove useful for the detection of botulinum neurotoxins in food and clinical samples.

• Molecules and Cells
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• 제38권8호
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• pp.669-676
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• 2015

Genome instability, primarily caused by faulty DNA repair mechanisms, drives tumorigenesis. Therapeutic interventions that exploit deregulated DNA repair in cancer have made considerable progress by targeting tumor-specific alterations of DNA repair factors, which either induces synthetic lethality or augments the efficacy of conventional chemotherapy and radiotherapy. The study of Fanconianemia (FA), a rare inherited blood disorder and cancer predisposition syndrome, has been instrumental in understanding the extent to which DNA repair defects contribute to tumorigenesis. The FA pathway functions to resolve blocked replication forks in response to DNA interstrand cross-links (ICLs), and accumulating knowledge of its activation by the ubiquitin-mediated signaling pathway has provided promising therapeutic opportunities for cancer treatment. Here, we discuss recent advances in our understanding of FA pathway regulation and its potential application for designing tailored therapeutics that take advantage of deregulated DNA ICL repair in cancer.

• BMB Reports
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• 제55권12호
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• pp.645-650
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• 2022

Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

• 한국응용과학기술학회지
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• 제35권1호
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• pp.284-291
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• 2018

본 연구에서는 식품 및 화장품 원료로 널리 사용되는 천연 다당류의 분자 구조, 분자량, 점도, 친수성, 팽창, 습윤 및 보습 특성을 이용하여 도로 분진 방지제를 제조하였다. 다양한 분진 제어 효과가 확인되었으며 단순한 물 분사 및 시험 대조군인 합성PVA보다 우수한 결과를 얻었다. 또한 수분증발 비교, 비산 저감율, 공사현장 테스트 및 물벼룩 급성 독성 시험 등의 영향을 연구하고 토양 및 수질의 안전성을 연구하여 도로 분진 방지제의 유용성을 확인하였다.

• 미생물학회지
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• 제50권3호
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• pp.249-253
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• 2014

THOC7/Mft1는 mRNA가 전사되는 동안 mRNP의 포장과 mRNA 방출에 관여하는 진화적으로 잘 보존된 THO 복합체의 구성인자이다. 분열효모 Schizosaccharomyces pombe에서 THOC7/Mft1의 이종상동체(spThoc7)가 합성치사 돌연변이체 SLRsm1의 생장 결함을 부분적으로 상보하는 것으로 선별되었다. 이배체 S. pombe 균주에 하나의 spthoc7 유전자만을 결실시킨 후 4분체 분석을 수행한 결과, 이 유전자는 생장에 필수적이지 않았다. 하지만, ${\Delta}thoc7$ 결실돌연변이는 생장과 mRNA의 핵에서 세포질로의 방출에 약간의 결함을 보였다. 기능을 하는 spThoc7-GFP단백질은 주로 핵 안에 존재하였다. 이와 같은 결과들은 spThoc7도 mRNA 방출에 관여하고 있음을 시사한다.