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Investigation of the Bovine Leukemia Virus Proviral DNA in Human Leukemias and Lung cancers in Korea
Lim Chul Joo,Han Kyungja,Oh Jae Ho,Hwang Myung Sil,Yum Young Na,Kim Sheen Hee,Shin Dong Hwan,Yang Ki Hwa,Kim Yonggoo,Kang Chang Suk,Cho Dae Hyun,Lee Jehoon 대한의학회 2005 Journal of Korean medical science Vol.20 No.4
PCNA Modifications for Regulation of Post-Replication Repair Pathways
Kyoo-young Lee,Kyungjae Myung 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.1
Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is catalyzed by Rad6/Rad18 complex. PCNA monoubiquitination triggers the replacement of replicative polymerase with special translesion synthesis (TLS) polymerases that are able to replicate past DNA lesions. The PCNA interaction motif and/or the ubiquitin binding motif in most TLS polymerases seem to be important for the regulation of TLS. The TLS pathway is usually error-prone because TLS polymerases have low fidelity and no proofreading activity. PCNA can also be further polyubiquitinated by Ubc13/ Mms2/Rad5 complex, which adds an ubiquitin chain onto monoubiquitinated K164 of PCNA. PCNA polyubiquitination directs a different PRR pathway known as error-free damage avoidance, which uses the newly synthesized sister chromatid as a template to bypass DNA damage presumably through template switching mechanism. Mammalian homologues of all of the yeast PRR proteins have been identified, thus PRR is well conserved throughout evolution. Mutations of some PRR genes are associated with a higher risk for cancers in mice and human patients, strongly supporting the importance of PRR as a tumor suppressor pathway.
Kuram, Malleswara Rao,Kim, Woo Gyum,Myung, Kyungjae,Hong, Sung You WILEY‐VCH Verlag 2016 EUROPEAN JOURNAL OF ORGANIC CHEMISTRY Vol.3 No.-
<P>Herein, we report the first Cu-catalyzed one-step method for the synthesis of 1,2,4-oxadiazoles from stable, less toxic, and readily available amides and organic nitriles by a rare oxidative N-O bond formation using O-2 as sole oxidant. This method has a broad substrate scope and a good tolerance for diverse functional groups. Moreover, the synthetic utility of this method is highlighted by the synthesis of biologically active 3,5-disubstituted derivatives.</P>
Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions
Sinha, Supriya,Li, Fuyang,Villarreal, Diana,Shim, Jae Hoon,Yoon, Suhyeon,Myung, Kyungjae,Shim, Eun Yong,Lee, Sang Eun Public Library of Science 2017 PLoS genetics Vol.13 No.4
<▼1><P>Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal rearrangements but its role in mutagenesis has not yet been analyzed. Here we determined the mutation frequency of a <I>URA3</I> reporter gene placed at multiple locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203-bp) of direct repeat sequences for efficient repair in budding yeast. Induction of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled to its slower repair kinetics and the extensive resection occurring at flanking DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking DNA sequences 7.1 kb distal to the breakpoint junction as compared to those without MH. The results suggest that MMEJ could destabilize genomes by triggering structural alterations and increasing mutation burden.</P></▼1><▼2><P><B>Author summary</B></P><P>Recurrent chromosome translocations juxtapose chromosomal fragments and alter expression of tumor suppressors or oncogenes at or near breakpoint junctions to develop distinct types of leukemias and childhood sarcomas. The prevalence of 2–20 bp of imperfect overlapping sequences (a.k.a. microhomology [MH]) at the breakpoint junctions suggests the type of repair events joining two chromosomal fragments and the formation of oncogenic chromosomal translocations. In this study, we discovered that MH-mediated end joining (MMEJ) operates with kinetics markedly slower than other repair options. The slower kinetics leads to extensive resection and drives hypermutagenesis at sequences flanking the break site. We also found that MH-mediated chromosomal translocations accumulate mutations at sequences up to several kilobases distal to the breakpoint junction as compared to those without MH. Our results revealed that MH contributes to genetic instability by facilitating chromosomal translocations and increasing mutational load at the sequences flanking the breakpoints.</P></▼2>
Tissue-specific DNA damage response in Mouse Whole-body irradiation
Lee Seon-Gyeong,Kim Namwoo,박인배,Park Jun Hong,Myung Kyungjae 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.1
Background Genomic instability is a hallmark of various cancers, and DNA repair is an essential process for maintaining genomic integrity. Mammalian cells have developed various DNA repair mechanisms in response to DNA damage. Compared to the cellular response to DNA damage, the in vivo DNA damage response (DDR) of specific tissues has not been studied extensively. Objective In this study, mice were exposed to whole-body gamma (γ)-irradiation to evaluate the specific DDR of various tissues. We treated male C57BL6/J mice with γ-irradiation at different doses, and the DDR protein levels in different tissues were analyzed. Results The level of gamma-H2A histone family member X (γH2AX) increased in most organs after exposure to γ-irradiation. In particular, the liver, lung, and kidney tissues showed higher γH2AX induction upon DNA damage, compared to that in the brain, muscle, and testis tissues. RAD51 was highly expressed in the testis, irrespective of irradiation. The levels of proliferating cell nuclear antigen (PCNA) and ubiquitinated PCNA increased in lung tissues upon irradiation, suggesting that the post-replication repair may mainly operate in the lungs in response to γ-irradiation. Conclusion These results suggest that each tissue has a preferable repair mechanism in response to γ-irradiation. Therefore, the understanding and application of tissue-specific DNA damage responses could improve the clinical approach of radiotherapy for treating specific cancers.
윤지희,임동술,Jin-Yang Kang,Byung-Yong Kang,Eun-ah Shin,Myung-Jun Chung,Soo-Dong Kim,Dae-Heoun Baek,Kyungjae Kim,하남주 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.6
The intestinal microbiota are important to the host with regard to resistance they impart against bacterial infections and their involvement in mediating metabolic functions. Lactic acid producing bacteria such as Lactobacillus play an important physiological role in these matters. The aim of the present study was to isolate Lactobacillus sp. that inhibits enteric pathogens. Initially, 17 isolates from healthy Koreans were collected on Lactobacillus selective medium. Resistance of the isolates to antibiotics including rifampicin, streptomycin, clindamycin and vancomycin was measured. One of the isolate was identified as Lactobacillus ruminus on the basis of bacterial cell morphology, cultural characteristic and biochemical characteristics, 16S rRNA sequence analysis and PCR-RAPD. Antimicrobial activity of the bacterium against Vancomycin Intermediate Resistant Staphylococcus aureus (VISA) and Vancomycin-Resistant Enterococci (VRE) was measured. About 104 cells of VISA or VRE were mixed with 1, 5, and 9 mL of L. ruminus SPM 0211 and the final volume was adjusted to 10 mL with brain heart infusion (BHI) broth. The cell suspension was incubated for 3, 6, 9, and 24 h, serially diluted and then plated on BHI agar plates. As numbers of L. ruminus SPM 0211 were increased, viable cell count of VISA and VRE decreased. The strongest antimicrobial activity of SPM 0211 was observed after 9 h incubation in any mixture, almost completely inhibiting the growth of these two bacteria. The results suggest that the freshly isolated L. ruminus SPM 0211 may be used as a pro-biotic microbe that prevents the colonization of enteric pathogens and can thereby promote good gastrointestinal health.
Do Kyung Lee(이도경),Byung Yong Kang(강병용),Myung Jun Chung(정명준),Kang Oh Lee(이강오),Kyungjae Kim(김경제),Nam Joo Ha(하남주) 환경독성보건학회 2008 환경독성보건학회지 Vol.23 No.1
유산균인 비피도박테리아는 사람과 동물에서 유익한 프로바이오틱 미생물로 알려져 있다. 본 연구에서는 이러한 비피도박테리아 균주의 분류를 위한 repetitive DNA element PCR fingerprinting (ERIC-또는 TAP-PCR)의 사용을 평가하였다. 사람분변으로부터 분리한 알려지지 않은 비피도박테리움 균주와 한국생명공학연구원 생물자원센터로부터 분양받은 표준균주를 가지고 분류 및 동정에 ERIC-PCR과 TAP-PCR을 이용한 RAPD-fingerprinting을 수행하였다. 그 결과 비피도박테리움 균주에 대한 속과 종단위의 분류가 가능하였으며, 실험에 사용된 모든 비피도박테리움 균주는 RAPD-fingerprinting 분석을 통해 유전적 다양성을 확인하였다. 또한 ERIC2와 TAPI 프라이머를 이용한 실험에서는 Bifidobacterium adolescentis 특이 유전자 단편을 확인하였으며 이는 B. adolescentis 균주의 동정에 유용할 것으로 사료된다.