• Molecules and Cells
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• v.46 no.6
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• pp.374-386
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• 2023

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

• Molecules and Cells
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• v.38 no.9
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• pp.750-758
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• 2015

Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

• KSBB Journal
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• v.8 no.2
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• pp.133-142
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• 1993

The effects of genetic and environmental factors on productivity of a cloned protein were studied in recombinant Saccharomyces cerevisiae. Plasmid stability and copy level were very high for a $REP^+$ system(at ca. 10 generations, stability: 65-90%, plasmid copy number per cell: 40-200), whereas these were very low for a yep- system(at ca. 10 generations, stability: 30%, plasmid copy number per cell 20). In plasmids containing the $2{\mu}m$ circle genome, a $[cir^o]$ strain was a preferred host cell since the plasmid stability and the copy number in a $[cir^o]$ strain were higher than in a $[cir^+]$strain. Cloned gene expression was dependent on plasmid copy number and stability. The inducer (galactose) level played a very important role in cloned lacZ gene expression, showing that a galactose concentration of 0.8% was sufficient for induction of gene expression. Induction rate was very fast in the case of plasmids exhibiting high stability and copy number by a factor of 4 to 25. The time to reach the peak value of gene expression was longer when galactose was added at the start of fermentation (ca. 26 hours) than at the mid-exponential phase (ca. 6 hours). Glucose repression was reduced by a factor of 2 to 5 as the relative inducer level increased.

• Journal of Microbiology
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• v.44 no.5
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• pp.530-536
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• 2006

Bacteriophage P4, a satellite phage of coliphage P2, is a very useful experimental tool for the study of viral capsid assembly and cos-cleavage. For an in vitro cos-cleavage reaction study of the P2-P4 system, new shortened and selectable markers containing P4 derivative plasm ids were designed as a substrate molecules. They were constructed by swapping the non-essential segment of P4 DNA for either the kanamycin resistance (kmr) gene or the ampicillin resistance (apr) gene. The size of the genomes of the resulting markers were 82% (P4 ash8 delRI:: kmr) and 79% (P4 ash8 delRI:: apr) of the wild type P4 genome. To determine the lower limit of genome size that could be packaged into the small P4-size bead, these shortened P4 plasmids were converted to phage particles with infection of the helper phage P2. The conversion of plasmid P4 derivatives to bacteriophage particles was verified by the heat stability test and the burst size determination experiment. CsCl buoyant equilibrium density gradient experiments confirmed not only the genome size of the viable phage form of shortened P4 derivatives, but also their packaging into the small P4-size head. P4 ash8 delRI:: apr turned out to be the smallest P4 genome that can be packaged into P4-sized head.

• The Korean Journal of Food & Health Convergence
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• v.5 no.2
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• pp.27-34
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• 2019

RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.13-18
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• 2018

Objective: Meat quality including muscle color in chickens is an important trait and continuous selective pressures for fast growth and high yield have negatively impacted this trait. This study was conducted to investigate genetic variations responsible for regulating muscle color. Methods: Whole genome re-sequencing analysis using Illumina HiSeq paired end read method was performed with pooled DNA samples isolated from two broiler chicken lines divergently selected for muscle color (high muscle color [HMC] and low muscle color [LMC]) along with their random bred control line (RAN). Sequencing read data was aligned to the chicken reference genome sequence for Red Jungle Fowl (Galgal4) using reference based genome alignment with NGen program of the Lasergene software package. The potential causal single nucleotide polymorphisms (SNPs) showing non-synonymous changes in coding DNA sequence regions were chosen in each line. Bioinformatic analyses to interpret functions of genes retaining SNPs were performed using the ingenuity pathways analysis (IPA). Results: Millions of SNPs were identified and totally 2,884 SNPs (1,307 for HMC and 1,577 for LMC) showing >75% SNP rates could induce non-synonymous mutations in amino acid sequences. Of those, SNPs showing over 10 read depths yielded 15 more reliable SNPs including 1 for HMC and 14 for LMC. The IPA analyses suggested that meat color in chickens appeared to be associated with chromosomal DNA stability, the functions of ubiquitylation (UBC) and quality and quantity of various subtypes of collagens. Conclusion: In this study, various potential genetic markers showing amino acid changes were identified in differential meat color lines, that can be used for further animal selection strategy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5333-5338
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• 2012

Vitamin B6 functions as a coenzyme in >140 enzymatic reactions involved in the metabolism of amino acids, carbohydrates, neurotransmitters, and lipids. It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine ${\beta}$-synthase (CBS) and ${\gamma}$-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate-mediated one-carbon metabolism or the transsulfuration pathway. Folate cofactors carry and chemically activate single carbons for the synthesis of purines, thymidylate and methionine. So the evidence indicates that vitamin B6 plays an important role in maintenance of the genome, epigenetic stability and homocysteine metabolism. This article focuses on studies of strand breaks, micronuclei, or chromosomal aberrations regarding protective effects of vitamin B6, and probes whether it is folate-mediated one-carbon metabolism or the transsulfuration pathway for vitamin B6 which plays critical roles in prevention of cancer and cardiovascular disease.

• Molecules and Cells
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• v.37 no.2
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• pp.95-99
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• 2014

Cancer is unique amongst human diseases in that its cellular manifestations arise and evolve through the acquisition of somatic alterations in the genome. In particular, instability in the number and structure of chromosomes is a near-universal feature of the genomic alterations associated with epithelial cancers, and is triggered by the inactivation of tumour suppressor mechanisms that preserve chromosome integrity in normal cells. The nature of these mechanisms, and how their inactivation promotes carcinogenesis, remains enigmatic. I will review recent work from our laboratory on the tumour suppressor BRCA2 that addresses these issues, focusing on new insights into cancer pathogenesis and therapy that are emerging from improved understanding of the molecular basis of chromosomal instability in BRCA2-deficient cancer cells.

• Korean Journal of Microbiology
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• v.31 no.1
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• pp.37-43
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• 1993

The effect of stb locus of E. COLI IncFII plasmid NR1 on the stability of chimeric plasmids was investigated. First, we have isolated the stability locus (stb) from E. coli NR1 plasmid and then inserted into the three different vectors, pUC8, YRp17 and YEp24. By examining their stability in E. coli and yeast, we showed that the recombinant plasmids containing stb locus were resonably stable. Also, by comparing the amounts of the rDNA fragments per haploid genome with those of the plasmid fragments, we showed they copy number of recombinant plasmids was not increased. Consequently, the stb locus of E. coli IncFII plasmid NR1 stabilized the chimeric plasmids but did not affect the replication or copy number of plasmids.

• International Journal of Industrial Entomology and Biomaterials
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• v.36 no.1
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• pp.15-24
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• 2018

N-glycosylation is an important posttranslational modification that results in a variety of biological activities, structural stability, and protein-protein interactions. There are still many mysteries in the structure and function of N-glycans, and detailed elucidation is necessary. Baculovirus expression system (BES) is widely used to produce recombinant glycoproteins, but it is not suitable for clinical use due to differences in N-glycan structure between insects and mammals. It is necessary to develop adequate model glycoproteins for analysis to efficiently alter the insect-type N-glycosylation pathway to human type. The previous research shows the recombinant alpha 1-acid glycoprotein (${\alpha}1AGP$) secreted from silkworm cultured cells or larvae is highly glycosylated and expected to be an excellent research candidate for the glycoprotein analysis expressed by BES. Therefore, we improved the ${\alpha}1AGP$ to be a better model for studying glycosylation. The modified ${\alpha}1AGP$ (${\alpha}1AGP{\Delta}$) recombinant protein was successfully expressed and purified by using BES, however, the expression level in silkworm cultured cells and larvae were lower than that of the ${\alpha}1AGP$. Subsequently, we confirmed the detailed profile of N-glycan on the ${\alpha}1AGP{\Delta}$ by LS/MS analysis the N-glycan structure at each glycosylation site. These results indicated that the recombinant ${\alpha}1AGP{\Delta}$ could be usable as a better model glycoprotein of N-glycosylation research in BES.