Prof. Tae-Hong Kang, PhD - Dong-A University - Professor

Prof. Tae-Hong Kang

PhD

Dong-A University

Professor

Busan | Korea, Republic of

Main Specialties: Biochemical Genetics, Biology, Molecular Genetic Pathology, Oncology, Pharmacology

Additional Specialties: DNA damage response

ORCID logohttps://orcid.org/0000-0002-6013-900X


Top Author

Prof. Tae-Hong Kang, PhD - Dong-A University - Professor

Prof. Tae-Hong Kang

PhD

Introduction

Dr. Kang is an Associate Professor and Department Chair in the Department of Biological Sciences at Dong-A University. He earned his M.D. and Ph.D. from POSTECH (Pohang University of Science and Technology) Division of Life Science after receiving a Bachelor’s degree in Molecular Biology at the Pusan National University. He joined Dr. Aziz Sancar lab for his post-doctoral training in the Department of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill (UNC-CH). His post-doctoral work was focused on the control of DNA damage response (DDR) by the circadian clock. He discovered that nucleotide excision repair (NER) in the mouse brain is controlled by the clock. This finding generated great interest from the scientific community as well as the general public. Dr. Kang continued characterizing the phenomenon and he found that NER of cisplatin-DNA adducts exhibits circadian oscillation in most mouse tissues. In light of his work, a strong scientific foundation of chrono-modulated cancer therapy was established and it has been becoming an attractive option in clinics.
Currently, Dr. Kang is conducting further studies to elucidate the mechanistic aspects of circadian clock-DDR connection and its potential clinical applications. He is a recipient of several prizes for excellence of research from POSTECH, UNC-CH, KSMCB (Korean Society for Molecular and Cellular Biology), KSBMB (Korean Society for Biochemistry and Molecular Biology).

Primary Affiliation: Dong-A University - Busan , Korea, Republic of

Specialties:

Additional Specialties:

Research Interests:


View Prof. Tae-Hong Kang’s Resume / CV

Education

Feb 2020
UT Health Science Center San Antonio

Visiting Professor
Jan 2011
University of North Carolina at Chapel Hill
Post-Doctoral Training
Research Associate
Feb 2008
Pohang University of Science and Technology
Ph.D
Graduate Student
Feb 2001
Pusan National University
B.S
Undergraduate Student

Experience

Nov 2009
Postdoc Scholar Award for Research Excellence

UNC-CH
Oct 2008
Best Thesis Award

KSMCB
May 2008
Young Scientist Award

KSBMB
May 2007
FluoresScience Award

Carl Zeiss Korea
May 2007
Conference Award

FOBMB
Oct 2006
Best Thesis Award

POSTECH
May 2004
Best Research Award

KSBMB

Publications

31Publications

474Reads

33Profile Views

Posttranscriptional control of the replication stress response via TTP-mediated Claspin mRNA stabilization.

Oncogene 2020 Apr 21;39(16):3245-3257. Epub 2020 Feb 21.

Department of Biological Sciences, Dong-A University, Busan, 49315, South Korea.

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http://dx.doi.org/10.1038/s41388-020-1220-9DOI Listing
April 2020
8.459 Impact Factor

DNA Oxidation and Excision Repair Pathways.

Int J Mol Sci 2019 Dec 3;20(23). Epub 2019 Dec 3.

Department of Biological Science, Dong-A University, Busan 49315, Korea.

The physiological impact of the aberrant oxidation products on genomic DNA were demonstrated by embryonic lethality or the cancer susceptibility and/or neurological symptoms of animal impaired in the base excision repair (BER); the major pathway to maintain genomic integrity against non-bulky DNA oxidation. However, growing evidence suggests that other DNA repair pathways or factors that are not primarily associated with the classical BER pathway are also actively involved in the mitigation of oxidative assaults on the genomic DNA, according to the corresponding types of DNA oxidation. Among others, factors dedicated to lesion recognition in the nucleotide excision repair (NER) pathway have been shown to play eminent roles in the process of lesion recognition and stimulation of the enzyme activity of some sets of BER factors. Besides, substantial bulky DNA oxidation can be preferentially removed by a canonical NER mechanism; therefore, loss of function in the NER pathway shares common features arising from BER defects, including cancer predisposition and neurological disorders, although NER defects generally are nonlethal. Here we discuss recent achievements for delineating newly arising roles of NER lesion recognition factors to facilitate the BER process, and cooperative works of BER and NER pathways in response to the genotoxic oxidative stress.

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http://dx.doi.org/10.3390/ijms20236092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929053PMC
December 2019
4.183 Impact Factor

Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks.

Nat Commun 2019 04 5;10(1):1577. Epub 2019 Apr 5.

Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.

DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and ?H2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.

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http://dx.doi.org/10.1038/s41467-019-09641-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450972PMC
April 2019
5 Reads
11.878 Impact Factor

Roles of Tristetraprolin in Tumorigenesis.

Int J Mol Sci 2018 Oct 29;19(11). Epub 2018 Oct 29.

Department of Biological Science, Dong-A University, Busan 49315, Korea.

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed.

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http://dx.doi.org/10.3390/ijms19113384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274954PMC
October 2018
12 Reads
4.183 Impact Factor

Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation.

Int J Mol Sci 2016 Nov 4;17(11). Epub 2016 Nov 4.

Department of Biological Science, Dong-A University, Busan 49315, Korea.

Ultraviolet (UV) radiation from sunlight represents a constant threat to genome stability by generating modified DNA bases such as cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP). If unrepaired, these lesions can have deleterious effects, including skin cancer. Mammalian cells are able to neutralize UV-induced photolesions through nucleotide excision repair (NER). The NER pathway has multiple components including seven xeroderma pigmentosum (XP) proteins (XPA to XPG) and numerous auxiliary factors, including ataxia telangiectasia and Rad3-related (ATR) protein kinase and RCC1 like domain (RLD) and homologous to the E6-AP carboxyl terminus (HECT) domain containing E3 ubiquitin protein ligase 2 (HERC2). In this review we highlight recent data on the transcriptional and posttranslational regulation of NER activity.

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http://dx.doi.org/10.3390/ijms17111840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133840PMC
November 2016
1 Read
4.183 Impact Factor

Enhancement of UV-induced nucleotide excision repair activity upon forskolin treatment is cell growth-dependent.

BMB Rep 2016 Oct;49(10):566-571

Department of Biological Science, Dong-A University, Busan 49315, Korea.

Forskolin (FSK), an adenylyl cyclase activator, has recently been shown to enhance nucleotide excision repair (NER) upon UV exposure. However, our study revealed that this effect was detected in human skin epithelial ARPE19 cells only in growing cells, but not in non-cycling cells. When the cells were grown at low density (70% confluence), FSK was capable of stimulating cAMP responsive element binding (CREB) phosphorylation, a marker for FSK-stimulated PKA activation, and resulted in a significant increase of NER activity compared to control treatment. However, cells grown under 100% confluent conditions showed neither FSK-induced CREB phosphorylation nor the resulting NER enhancement. These findings indicate that cellular growth is critical for FSK-induced NER enhancement and suggest that cellular growth conditions should be considered as a variable while evaluating a reagent's pharmacotherapeutic efficacy. [BMB Reports 2016; 49(10): 566-571].

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227299PMC
http://dx.doi.org/10.5483/bmbrep.2016.49.10.097DOI Listing
October 2016
9 Reads
2.966 Impact Factor

A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility.

Exp Mol Med 2016 07 15;48(7):e246. Epub 2016 Jul 15.

Department of Biological Science, Dong-A University, Busan, Korea.

Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case-control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02-4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer.

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http://dx.doi.org/10.1038/emm.2016.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973313PMC
July 2016
17 Reads
4.743 Impact Factor

Non-thermal plasma-induced apoptosis is modulated by ATR- and PARP1-mediated DNA damage responses and circadian clock.

Oncotarget 2016 May;7(22):32980-9

Department of Biological Science, Dong-A University, Busan 604714, Republic of Korea.

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http://dx.doi.org/10.18632/oncotarget.9087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078068PMC
May 2016
6 Reads
6.359 Impact Factor

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer.

Clin Cancer Res 2015 Dec 12;21(23):5391-403. Epub 2015 Aug 12.

Department of Biological Science, Dong-A University, Busan, Republic of Korea.

Purpose: Previous study identified E2F1 as a key mediator of non-muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis and aggressive characteristics of bladder cancer.

Experimental Design: Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay.

Results: The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)-related genes.

Conclusions: The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1-EZH2-SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1-EZH2-SUZ12-driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities.

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http://dx.doi.org/10.1158/1078-0432.CCR-14-2680DOI Listing
December 2015
43 Reads
8.911 Impact Factor

Enhanced nucleotide excision repair capacity in lung cancer cells by preconditioning with DNA-damaging agents.

Oncotarget 2015 Sep;6(26):22575-86

Department of Biological Science, Dong-A University, Busan, Korea.

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http://dx.doi.org/10.18632/oncotarget.4610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673183PMC
September 2015
8 Reads
6.359 Impact Factor

NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair.

Biochem Biophys Res Commun 2015 Jun 22;461(3):543-8. Epub 2015 Apr 22.

Department of Biological Science, Dong-A University, Busan, South Korea. Electronic address:

Nucleotide excision repair (NER) is the sole mechanism of UV-induced DNA lesion repair in mammals. A single round of NER requires multiple components including seven core NER factors, xeroderma pigmentosum A-G (XPA-XPG), and many auxiliary effector proteins including ATR serine/threonine kinase. The XPA protein helps to verify DNA damage and thus plays a rate-limiting role in NER. Hence, the regulation of XPA is important for the entire NER kinetic. We found that NDR1, a novel XPA-interacting protein, modulates NER by modulating the UV-induced DNA-damage checkpoint. In quiescent cells, NDR1 localized mainly in the cytoplasm. After UV irradiation, NDR1 accumulated in the nucleus. The siRNA knockdown of NDR1 delayed the repair of UV-induced cyclobutane pyrimidine dimers in both normal cells and cancer cells. It did not, however, alter the expression levels or the chromatin association levels of the core NER factors following UV irradiation. Instead, the NDR1-depleted cells displayed reduced activity of ATR for some set of its substrates including CHK1 and p53, suggesting that NDR1 modulates NER indirectly via the ATR pathway.

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http://dx.doi.org/10.1016/j.bbrc.2015.04.071DOI Listing
June 2015
20 Reads
2.705 Impact Factor

Effect of additive oxygen gas on cellular response of lung cancer cells induced by atmospheric pressure helium plasma jet.

Sci Rep 2014 Oct 16;4:6638. Epub 2014 Oct 16.

Department of Biological Science, Dong-A University, Busan 604-714, Republic of Korea.

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http://dx.doi.org/10.1038/srep06638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198870PMC
October 2014
5 Reads
5.078 Impact Factor

Identification of lactoferrin as a human dedifferentiation factor through the studies of reptile tissue regeneration mechanisms.

J Microbiol Biotechnol 2014 Jun;24(6):869-78

Department of Biological Science, Dong-A University, Busan 604-714, Republic of Korea.

In this study, we performed two-dimensional electrophoresis with protein extracts from lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homolog of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation, at least partly by increasing the expression of Klf4.

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http://dx.doi.org/10.4014/jmb.1402.02009DOI Listing
June 2014
37 Reads
1.975 Impact Factor

Expression signature defined by FOXM1-CCNB1 activation predicts disease recurrence in non-muscle-invasive bladder cancer.

Clin Cancer Res 2014 Jun 8;20(12):3233-43. Epub 2014 Apr 8.

Authors' Affiliations: Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon; Department of Biology, College of Natural Science, Dong-A University, Busan; Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea; and Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

Purpose: Although standard treatment with transurethral resection and intravesical therapy (IVT) is known to be effective to address the clinical behavior of non-muscle-invasive bladder cancer (NMIBC), many patients fail to respond to the treatment and frequently experience disease recurrence. Here, we aim to identify a prognostic molecular signature that predicts the NMIBC heterogeneity and response to IVT.

Experimental Design: We analyzed the genomic profiles of 102 patients with NMIBC to identify a signature associated with disease recurrence. The validity of the signature was verified in three independent patient cohorts (n = 658). Various statistical methods, including a leave-one-out cross-validation and multivariate Cox regression analyses, were applied to identify a signature. We confirmed an association between the signature and tumor aggressiveness with experimental assays using bladder cancer cell lines.

Results: Gene expression profiling in 102 patients with NMIBC identified a CCNB1 signature associated with disease recurrence, which was validated in another three independent cohorts of 658 patients. The CCNB1 signature was shown to be an independent risk factor by a multivariate analysis and subset stratification according to stage and grade [HR, 2.93; 95% confidence intervals (CI), 1.302-6.594; P = 0.009]. The subset analysis also revealed that the signature could identify patients who would benefit from IVT. Finally, gene network analyses and experimental assays indicated that NMIBC recurrence could be mediated by FOXM1-CCNB1-Fanconi anemia pathways.

Conclusions: The CCNB1 signature represents a promising diagnostic tool to identify patients with NMIBC who have a high risk of recurrence and to predict response to IVT.

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http://dx.doi.org/10.1158/1078-0432.CCR-13-2761DOI Listing
June 2014
58 Reads
8.911 Impact Factor

Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1.

Nucleic Acids Res 2014 Apr 30;42(7):4427-34. Epub 2014 Jan 30.

Department of Biological Science, Dong-A University, Hadan2-dong, Saha-gu, Busan 604-714, South Korea.

Mammalian cryptochromes (Crys) are essential circadian clock factors implicated in diverse clock-independent physiological functions, including DNA damage responses. Here we show that Cry1 modulates the ATR-mediated DNA damage checkpoint (DDC) response by interacting with Timeless (Tim) in a time-of-day-dependent manner. The DDC capacity in response to UV irradiation showed a circadian rhythm. Interestingly, clock-deficient Cry1 and Cry2 double knockout (Cry(DKO)) cells retained substantial DDC capacity compared with clock-proficient wild-type cells, although the Cry1-modulated oscillation of the DDC capacity was abolished in Cry(DKO) cells. We found temporal interaction of Cry1 and Tim in the nucleus. When Cry1 was expressed in the nucleus, it was critical for circadian ATR activity. We regenerated rhythmic DDC responses by ectopically expressing Cry1 in Cry(DKO) cells. In addition, we also investigated the DDC capacity in the liver of mice that were intraperitoneally injected with cisplatin at different circadian times (CT). When mice were injected at CT20, about 2-fold higher expression of phosphorylated minichromosome maintenance protein 2 (p-MCM2) was detected compared with mice injected at CT08, which consequently affected the removal rate of cisplatin-DNA adducts from genomic DNA. Taken together, our data demonstrate the intimate interaction between the circadian clock and the DDC system during genotoxic stress in clock-ticking cells.

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http://dx.doi.org/10.1093/nar/gku094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985666PMC
April 2014
7 Reads
11.147 Impact Factor

Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair.

Oncogene 2014 Jan 26;33(1):19-25. Epub 2012 Nov 26.

Department of Biological Science, Dong-A University, Busan, Republic of Korea.

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http://dx.doi.org/10.1038/onc.2012.539DOI Listing
January 2014
8.459 Impact Factor

Tristetraprolin suppresses AHRR expression through mRNA destabilization.

FEBS Lett 2013 May 11;587(10):1518-23. Epub 2013 Apr 11.

Department of Biological Science, Dong-A University, Busan 604-714, Republic of Korea.

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http://dx.doi.org/10.1016/j.febslet.2013.03.031DOI Listing
May 2013
24 Reads
3.169 Impact Factor

Mitogen-activated protein kinase phosphatase 2 regulates histone H3 phosphorylation via interaction with vaccinia-related kinase 1.

Mol Biol Cell 2013 Feb 5;24(3):373-84. Epub 2012 Dec 5.

Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.

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http://dx.doi.org/10.1091/mbc.E12-06-0456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564537PMC
February 2013
19 Reads
4.466 Impact Factor

Association of MUC6-minisatellite variants with susceptibility to rectal carcinoma.

Mol Biol Rep 2013 Jan 10;40(1):303-8. Epub 2012 Oct 10.

Department of Biological Science, Dong-A University, 840 Hadan-2-dong, Saha-gu, Busan 604-714, Korea.

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http://dx.doi.org/10.1007/s11033-012-2062-5DOI Listing
January 2013
41 Reads
2.024 Impact Factor

Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3-Kinase/Akt Pathway.

Korean J Physiol Pharmacol 2012 Oct 18;16(5):361-5. Epub 2012 Oct 18.

Department of Biological Science, Dong-A University, Busan 604-714, Korea.

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http://dx.doi.org/10.4196/kjpp.2012.16.5.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484523PMC
October 2012
7 Reads
1.262 Impact Factor

Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein.

Nucleic Acids Res 2011 Apr 30;39(8):3176-87. Epub 2010 Dec 30.

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

The XPA (Xeroderma pigmentosum A) protein is one of the six core factors of the human nucleotide excision repair system. In this study we show that XPA is a rate-limiting factor in all human cell lines tested, including a normal human fibroblast cell line. The level of XPA is controlled at the transcriptional level by the molecular circadian clock and at the post-translational level by a HECT domain family E3 ubiquitin ligase called HERC2. Stabilization of XPA by downregulation of HERC2 moderately enhances excision repair activity. Conversely, downregulation of XPA by siRNA reduces excision repair activity in proportion to the level of XPA. Ubiquitination and proteolysis of XPA are inhibited by DNA damage that promotes tight association of the protein with chromatin and its dissociation from the HERC2 E3 ligase. Finally, in agreement with a recent report, we find that XPA is post-translationally modified by acetylation. However, contrary to the previous claim, we find that in mouse liver only a small fraction of XPA is acetylated and that downregulation of SIRT1 deacetylase in two human cell lines does not affect the overall repair rate. Collectively, the data reveal that XPA is a limiting factor in excision repair and that its level is coordinately regulated by the circadian clock, the ubiquitin-proteasome system and DNA damage.

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https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/
Publisher Site
http://dx.doi.org/10.1093/nar/gkq1318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082913PMC
April 2011
24 Reads
11.147 Impact Factor

Circadian clock control of the cellular response to DNA damage.

FEBS Lett 2010 Jun 15;584(12):2618-25. Epub 2010 Mar 15.

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA.

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http://doi.wiley.com/10.1016/j.febslet.2010.03.017
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http://dx.doi.org/10.1016/j.febslet.2010.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878924PMC
June 2010
27 Reads
3.169 Impact Factor

Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress.

J Biol Chem 2010 May 15;285(22):16562-71. Epub 2010 Mar 15.

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.

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http://www.jbc.org/lookup/doi/10.1074/jbc.M110.110304
Publisher Site
http://dx.doi.org/10.1074/jbc.M110.110304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878033PMC
May 2010
29 Reads
4.573 Impact Factor

Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase.

Proc Natl Acad Sci U S A 2010 Mar;107(11):4890-5

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

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http://dx.doi.org/10.1073/pnas.0915085107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841896PMC
March 2010
20 Reads
9.809 Impact Factor

Circadian regulation of DNA excision repair: implications for chrono-chemotherapy.

Cell Cycle 2009 Jun 9;8(11):1665-7. Epub 2009 Jun 9.

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

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http://www.tandfonline.com/doi/abs/10.4161/cc.8.11.8707
Publisher Site
http://dx.doi.org/10.4161/cc.8.11.8707DOI Listing
June 2009
5 Reads

Circadian oscillation of nucleotide excision repair in mammalian brain.

Proc Natl Acad Sci U S A 2009 Feb 21;106(8):2864-7. Epub 2009 Jan 21.

Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

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http://dx.doi.org/10.1073/pnas.0812638106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629438PMC
February 2009
16 Reads
9.809 Impact Factor

VRK1 phosphorylates CREB and mediates CCND1 expression.

J Cell Sci 2008 Sep 19;121(Pt 18):3035-41. Epub 2008 Aug 19.

Department of Life Science, Pohang University of Science and Technology , Pohang 790-784, Republic of Korea.

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http://jcs.biologists.org/cgi/doi/10.1242/jcs.026757
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http://dx.doi.org/10.1242/jcs.026757DOI Listing
September 2008
2 Reads
5.432 Impact Factor

VRK3-mediated inactivation of ERK signaling in adult and embryonic rodent tissues.

Biochim Biophys Acta 2008 Jan 4;1783(1):49-58. Epub 2007 Nov 4.

Department of Life Science, Biotechnology Research Center, Division of Molecular and Life Science, Pohang University of Science and Technology (POSTECH), San-31, Hyoja-Dong, Pohang, 790-784, Republic of Korea.

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http://dx.doi.org/10.1016/j.bbamcr.2007.10.011DOI Listing
January 2008
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Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells.

Mol Cell Biol 2007 Dec 15;27(24):8533-46. Epub 2007 Oct 15.

Department of Life Science, Division of Molecular & Life Science, Pohang University of Science and Technology, San-31, Hyoja-Dong, Pohang 790-784, Republic of Korea.

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http://dx.doi.org/10.1128/MCB.00018-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169395PMC
December 2007
6 Reads
4.777 Impact Factor

Negative regulation of ERK activity by VRK3-mediated activation of VHR phosphatase.

Nat Cell Biol 2006 Aug 16;8(8):863-9. Epub 2006 Jul 16.

Department of Life Science, Biotechnology Research Center, Division of Molecular and Life Science, Pohang University of Science and Technology (POSTECH), San-31, Hyoja-Dong, Pohang, 790-784, Republic of Korea.

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http://dx.doi.org/10.1038/ncb1447DOI Listing
August 2006
2 Reads
19.679 Impact Factor

Highly efficient protein expression and purification using bacterial hemoglobin fusion vector.

Plasmid 2005 May 20;53(3):274-82. Epub 2005 Jan 20.

X-ray Research Group, Pohang Accelerator Laboratory, Pohang, Kyungbuk 790-784, Republic of Korea.

Recently developed bacterial hemoglobin (VHb) fusion expression vector has been widely used for the production of many target proteins due to its distinctive properties of expressing fusion protein with red color which facilitates visualization of the steps in purification, and increasing solubility of the target proteins. However, after intensive use of the vector, several defects have been found. In this report, we present a modified VHb fusion vector (pPosKJ) with higher efficiency, in which most of the defects were eliminated. First, it was found that thrombin protease often digests target protein as well as inserted thrombin cleavage site, so it was replaced by a TEV cleavage site for more specific cleavage of VHb from target protein. Second, a glycine-rich linker sequence was inserted between 6x his-tag and VHb to improve the affinity of 6x his-tag to Ni-NTA resin, resulting in higher purity of eluted fusion protein. Third, EcoRI and XhoI restriction sites located elsewhere in the vector were removed to make these restriction sites available for the cloning of target protein coding genes. A pPosKJ vector was fully examined with an anti-apoptotic BCL-2 family member of Caenorhabditis elegans, CED-9. A C-terminal VHb fusion expression vector (pPosKJC) was also constructed for stable expression of target proteins that may be difficult to express with an N-terminal fusion. Vaccinia-related kinase 1 (VRK1) was also successfully expressed and purified using the vector with high yield. Taken together, we suggest that the VHb fusion vector may be well suited for high-throughput protein expression and purification.

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http://dx.doi.org/10.1016/j.plasmid.2004.11.006DOI Listing
May 2005
23 Reads
2.577 Impact Factor

Top co-authors

Jeong-Min Park
Jeong-Min Park

Konyang University Hospital

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Jin Woong Chung
Jin Woong Chung

Korea Research Institute of Bioscience and Biotechnology

7
Aziz Sancar
Aziz Sancar

University of North Carolina School of Medicine

6
Kyong-Tai Kim
Kyong-Tai Kim

Pohang University of Science and Technology

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Ji Ye Choi
Ji Ye Choi

Korea Advanced Institute of Science and Technology (KAIST)

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Joyce T Reardon
Joyce T Reardon

University of North Carolina School of Medicine

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Yun-Gil Roh
Yun-Gil Roh

Dong-A University

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Tae-Hee Lee
Tae-Hee Lee

University Park

3