• Molecules and Cells
• /
• v.41 no.8
• /
• pp.799-807
• /
• 2018

Emerging evidence has suggested that cellular crosstalk between RNF168 and poly(ADP-ribose) polymerase 1 (PARP1) contributes to the precise control of the DNA damage response (DDR). However, the direct and reciprocal functional link between them remains unclear. In this report, we identified that RNF168 ubiquitinates PARP1 via direct interaction and accelerates PARP1 degradation in the presence of poly (ADP-ribose) (PAR) chains, metabolites of activated PARP1. Through mass spectrometric analysis, we revealed that RNF168 ubiquitinated multiple lysine residues on PARP1 via K48-linked ubiquitin chain formation. Consistent with this, micro-irradiation-induced PARP1 accumulation at damaged chromatin was significantly increased by knockdown of endogenous RNF168. In addition, it was confirmed that abnormal changes of HR and HNEJ due to knockdown of RNF168 were restored by overexpression of WT RNF168 but not by reintroduction of mutants lacking E3 ligase activity or PAR binding ability. The comet assay also revealed that both PAR-binding and ubiquitin-conjugation activities are indispensable for the RNF168-mediated DNA repair process. Taken together, our results suggest that RNF168 acts as a counterpart of PARP1 in DDR and regulates the HR/NHEJ repair processes through the ubiquitination of PARP1.

• Journal of Preventive Medicine and Public Health
• /
• v.40 no.2
• /
• pp.122-129
• /
• 2007

During the last decade, genomic cohort study has been developed in many countries by linking health data and genetic data in stored samples. Genomic cohort study is expected to find key genetic components that contribute to common diseases, thereby promising great advance in genome medicine. While many countries endeavor to build biobank systems, biobank-based genome research has raised important ethical concerns including genetic privacy, confidentiality, discrimination, and informed consent. Informed consent for biobank poses an important question: whether true informed consent is possible in population-based genomic cohort research where the nature of future studies is unforeseeable when consent is obtained. Due to the sensitive character of genetic information, protecting privacy and keeping confidentiality become important topics. To minimize ethical problems and achieve scientific goals to its maximum degree, each country strives to build population-based genomic cohort research project, by organizing public consultation, trying public and expert consensus in research, and providing safeguards to protect privacy and confidentiality.

• BMB Reports
• /
• v.38 no.6
• /
• pp.725-738
• /
• 2005

Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a $1\;{\mu}M$ imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.

• The Journal of the Korean Society for Microbiology
• /
• v.34 no.6
• /
• pp.519-532
• /
• 1999

Helicobacter pylori is a causative agent of type B gastritis and plays a central role in the pathogenesis of gastroduodenal ulcer and gastric cancer. To elucidate the host-parasite relationship of the H. pylori infection on the basis of molecular biology, we tried to evaluate the genomic diversity of H. pylori. An ordered overlapping bacterial artificial chromosome (BAC) library of a Korean isolate, H. pylori 51 was constructed to set up a genomic map. A circular physical map was constructed by aligning ApaI, NotI and SfiI-digested chromosomal DNA. When the physical map of H. pylori 51 was compared to that of unrelated strain, H. pylori 26695, completely different restriction patterns were shown. Fifteen known genes were mapped on the chromosome of H. pylori 51 and the genetic map was compared with those of strain 26695 and J99, of which the entire genomic sequences were reported. There were some variability in the gene location as well as gene order among three strains. For further analysis on the genomic diversity of H. pylori, when comparing the genomic structure of 150 H. pylori Korean isolates with one another, genomic macrodiversity of H. pylori was characterized by several features: whether or not susceptible to restriction digestion of the chromsome, variation in chromosomal restriction fingerprint and/or high frequency of gene rearrangement. We also examined the extent of allelic variation in nucleotide or deduced amino acid sequences at the individual gene level. fucT, cagA and vacA were confirmed to carry regions of high variation in nucleotide sequence among strains. The plasticity zone and strain-specific genes of H. pylori 51 were analyzed and compared with the former two genomic sequences. It should be noted that the H. pylori 51-specific sequences were dispersed on the chromosome, not congregated in the plasticity zone unlike J99- or 26695-specific genes, suggesting the high frequency of gene rearrangement in H. pylori genome. The genome of H. pylori 51 shows differences in the overall genomic organization, gene order, and even in the nucleotide sequences among the H. pylori strains, which are far greater than the differences reported on the genomic diversity of H. pylori.

• The Journal of the Korean Society for Microbiology
• /
• v.35 no.1
• /
• pp.69-76
• /
• 2000

Members of the genus Acinetobacter are recognized as newer pathogens of the nosocomial infection with an increasing frequency in recent years. Strains that belonged to A. calcoaceticus A. baumannii complex (genomic species 1, 2, 3, and 13TU) were major groups associated with nosocomial infection. Phenotypic identification was unreliable and laborious method to classify Acinetobacter strains into 19 genomic species. Rapid and reliable identification of clinical isolates is essential to diagnosis and epidemiology of Acinetobacter. We investigated the suitability of amplified ribosomal DNA restriction analysis (ARDRA) to identify genomic species of 131 Acinetobacter isolates. The 16S rRNA genes (ribosomal DNA) were enzymatically amplified and the amplified PCR products were restricted independently with the enzymes, AluI, CfoI, and MboI. Genomic species of Acinetobacter was classified by the combinations of restriction patterns. The analysis was showed that restriction profiles were characteristic for each genomic species. One hundred fourteen isolates were identified as A. baumannii, twelve were identified as genomic species 13TU, and one was identified as genomic species 3. Four isolates were found to be unknown organisms. All of the isolates which were identified to A. baumannii by phenotypic tests were completely discriminated into A. baumannii and genomic species 13TU by ARDRA. This study demonstrates that ARDRA is a rapid and simple techniques for the identification of Acinetobacter species according to the genomic species.

• Molecules and Cells
• /
• v.46 no.1
• /
• pp.57-64
• /
• 2023

In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3' end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3' ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3'UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered "apparent" APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.

• BMB Reports
• /
• v.43 no.10
• /
• pp.643-648
• /
• 2010

Sir William Osler (1849-1919) recognized that "variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions we know as disease". Accordingly, the traditional methods of medicine are not always best for all patients. Over the last decade, the study of genomes and their derivatives (RNA, protein and metabolite) has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genomic tools such as sequence variation, transcription and, more recently, personal genome sequencing enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow. In addition, full application of personalized or genomic medicine requires dramatic changes in regulatory and reimbursement policies as well as legislative protection related to privacy. This review aims to provide a general overview of these topics in the field of personalized medicine.

• BMB Reports
• /
• v.57 no.1
• /
• pp.1-1
• /
• 2024

• Journal of Preventive Medicine and Public Health
• /
• v.42 no.6
• /
• pp.349-355
• /
• 2009

Biomarkers are characteristic biological properties that can be detected and measured in a variety of biological matrices in the human body, including the blood and tissue, to give an indication of whether there is a threat of disease, if a disease already exists, or how such a disease may develop in an individual case. Along the continuum from exposure to clinical disease and progression, exposure, internal dose, biologically effective dose, early biological effect, altered structure and/or function, clinical disease, and disease progression can potentially be observed and quantified using biomarkers. While the traditional discovery of biomarkers has been a slow process, the advent of molecular and genomic medicine has resulted in explosive growth in the discovery of new biomarkers. In this review, issues in evaluating biomarkers will be discussed and the biomarkers of environmental exposure, early biologic effect, and susceptibility identified and validated in epidemiological studies will be summarized. The spectrum of genomic approaches currently used to identify and apply biomarkers and strategies to validate genomic biomarkers will also be discussed.

• Genomics & Informatics
• /
• v.2 no.3
• /
• pp.126-130
• /
• 2004

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorph isms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.