Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease

Jin, Hyeonseok,Roy, Upasana,Lee, Gwangrog,Scharer, Orlando D.,Cho, Yunje American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.17

<P>DNA interstrand cross-links (ICLs) block the progress of the replication and transcription machineries and can weaken chromosomal stability, resulting in various diseases. FANCD2-FANCI-associated nuclease (FAN1) is a conserved structure-specific nuclease that unhooks DNA ICLs independently of the Fanconi anemia pathway. Recent structural studies have proposed two different mechanistic features for ICL unhooking by human FAN1: a specific basic pocket that recognizes the terminal phosphate of a 1-nucleotide (nt) 5 flap or FAN1 dimerization. Herein, we show that despite lacking these features, Pseudomonas aeruginosa FAN1 (PaFAN1) cleaves substrates at approximate to 3-nt intervals and resolves ICLs. Crystal structures of PaFAN1 bound to various DNA substrates revealed that its conserved basic Arg/Lys patch comprising Arg-228 and Lys-260 recognizes phosphate groups near the 5 terminus of a DNA substrate with a 1-nt flap or a nick. Substitution of Lys-260 did not affect PaFAN1's initial endonuclease activity but significantly decreased its subsequent exonuclease activity and ICL unhooking. The Arg/Lys patch also interacted with phosphates at a 3-nt gap, and this interaction could drive movement of the scissile phosphates into the PaFAN1-active site. In human FAN1, the ICL-resolving activity was not affected by individual disruption of the Arg/Lys patch or basic pocket. However, simultaneous substitution of both FAN1 regions significantly reduced its ICL-resolving activity, suggesting that these two basic regions play a complementary role in ICL repair. On the basis of these findings, we propose a conserved role for two basic regions in FAN1 to guide ICL unhooking and to maintain genomic stability.</P>

Structural and functional relationships of FAN1

Jin, Hyeonseok,Cho, Yunje Elsevier 2017 DNA repair Vol.56 No.-

<P><B>Abstract</B></P> <P>FANCD2/FANCI-associated nuclease (FAN1) is a 5′ flap structure-specific endonuclease and 5′ to 3′ exonuclease. This nuclease can resolve interstrand cross-links (ICLs) independently of the Fanconi anemia (FA) pathway and controls the progression of stalled replication forks in an FA-dependent manner, thereby maintaining chromosomal stability. Several FAN1 mutations are observed in various cancers and degenerative diseases. Recently, several crystal structures of the FAN1-DNA complexes have been reported, and to date, these represent the only structures for a DNA bound ICL-repair nuclease. Puzzlingly, human FAN1 forms two different quaternary structures with different DNA binding modes, and based on these structures, two ICL-repair mechanisms have been proposed. In one mechanism, monomeric FAN1 recognizes the 5′ flap terminal phosphate via a basic pocket and successively cleaves at every third nucleotide of the DNA substrates. In the other mechanism, dimeric FAN1 scans, latches, and unwinds the postnick duplex of the substrate DNA to direct the scissile phosphodiester group to the active site. In this review, we discuss the structures, function, and proposed mechanisms of FAN1 nuclease, and provide the insights into its role in ICL repair and in processing of stalled replication forks.</P>

Purification, crystallization, and X-ray crystallographic analysis of Nit2 from Kluyveromyces lactis

Chaewon Jin,Hyeonseok Jin,Bradley Quade,Jeong Ho Chang 한국구조생물학회 2020 Biodesign Vol.8 No.1

The nitrilase-like (NIT) protein subfamily is a member of the nitrilase superfamily, which exhibits CN hydrolase activity. NIT proteins are highly conserved, and mammals have Nit1 and Nit2. Nit proteins are putative tumor suppressors; however, the enzymatic activities of Nit1 and Nit2 are different. Nit1 is a metabolite repair enzyme, whereas Nit2 is an ω-amidase. In this study, in order to understand the structural features and functional diversity of Nit proteins, Nit2 from Kluyveromyces lactis was crystallized, and X-ray diffraction data were obtained at a resolution of 2.2 Å. The crystal of K. lactis Nit2 (KlNit2) belonged to the space group C2, with the unit cell parameters a = 79.0 Å, b = 211.1 Å, c = 89.4 Å, α = γ = 90°, β = 112.1°. The crystal contained four macromolecules in the asymmetric unit.

The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment

Jin Bong Choi,Kang Jun Cho,Joon Chul Kim,Chung Ho Kim,Yong-An Chung,Hyeonseok S. Jeong,Yong Soo Shim,Jun Sung Koh 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.3

Objective: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. Methods: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. Results: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). Conclusion: The results of this prospective clinical study suggest that daily use of tadalafil 5 m

KTX’s Interior Noise Reduction Performance Comparison for Each Section using Multichannel Active Noise Control

HyeonSeok Jang,Young Min Kim,Jin-Do Chung,Kwon Soon Lee 제어로봇시스템학회 2012 제어로봇시스템학회 국제학술대회 논문집 Vol.2012 No.10

Since the eco-era is getting closer, the importance of noise reducing in the passenger cars of high-speed train is very important. The active noise is best choice to reduce low frequency noise because since the passive one too heavy for high speed trains where weight so critical. Also ANC able to reduce the ambient noise when the environmentalfactor changes. To reduce a three-dimensional closed-space sound field like a car of a high-speed rail is hard to do using single channel ANC control system.

Resistive Sensors Based on Conducting Polypyrrole nanotubes

Jin-Yong Hong,Hyeonseok Yoon,Jyongsik Jang 한국고분자학회 2006 한국고분자학회 학술대회 연구논문 초록집 Vol.2006 No.10

Charge-Transport Behavior in Shape-Controlled Poly(3,4-ethylenedioxythiophene) Nanomaterials: Intrinsic and Extrinsic Factors

Yoon, Hyeonseok,Hong, Jin-Yong,Jang, Jyongsik WILEY-VCH Verlag 2007 Small Vol.3 No.10

<P>The charge-transport behavior in one-dimensional (1D) poly (3,4-ethylenedioxythiophene) (PEDOT) nanomaterials of three different shapes is described. Both intrinsic and extrinsic factors are considered from the viewpoint of a single nanoparticle and nanoparticle assembly. Intrinsically, the oxidation level of the 1D PEDOT nanomaterials becomes higher with increasing aspect ratio of the nanomaterials, which is closely linked to the conjugation length. This result implies that the transport properties of the nanomaterials are significantly dependent on their shape. Extrinsically, the 1D PEDOT nanomaterials make an ohmic contact with gold interdigitated microelectrodes. In addition, a strong correlation is observed between the interparticle contact resistance and the shape of the nanomaterials. Lastly, the intrinsic and extrinsic factors related to charge transport are further illustrated by the resistance changes of nanomaterial-based chemical sensors. As a result, judicious tailoring of the dimensional and geometrical characteristics of the conducting-polymer nanomaterials may enable precise control over their transport properties as well as the characteristics of the nanomaterial-based devices.</P> <B>Graphic Abstract</B> <P>Shaping up: Significant factors governing the charge-transport behavior in one-dimensional conducting-polymer nanomaterials of different shapes (nanoellipsoids, nanorods, and nanotubes) are systematically investigated. Their influences on the performance of sensor devices, such as interdigitated microelectrodes (see picture), are also examined. <img src='wiley_img/16136810-2007-3-10-SMLL200700245-content.gif' alt='wiley_img/16136810-2007-3-10-SMLL200700245-content'> </P>

수도권 고속철도 개통 이후 구간별 통행패턴 변화 예측

송현석(Hyeonseok Song),이주연(Ju Yeon Lee),최진석(Jin-seok Choi) 한국철도학회 2016 한국철도학회 학술발표대회논문집 Vol.2016 No.10

수도권 고속철도는 서울 수서에서 경기 평택까지 61.1km 구간을 고속신선으로 건설하는 사업으로 선로용량의 한계에 다다른 경부선 서울-시흥구간의 혼잡 해소와 서울역과 용산역에 집중되어있는 고속철도 서비스를 서울 강남, 강동, 수도권 동남부지역까지 확대하여 광역 및 지역간 통행시간 단축을 목적으로 하고 있다. 수도권 고속철도 운영사인 ㈜SR은 수서-부산, 수서-목포 노선을 2016년 12월 중으로 운영할 예정이다. 한국교통연구원에서는 수도권 고속철도 이용의사 설문조사를 서울역, 용산역, 광명역, 강남고속버스터미널에서 고속버스 및 고속철도 노선 이용자 2,109명을 대상으로 실시하였다. 본 연구에서는 조사 결과를 활용하여 지역간 통행에서 고속철도 및 고속버스 이용자들이 수도권 고속철도를 이용하여 발생하는 통행패턴 변화를 예측하고자 한다. Metropolitan Area High Speed Railway(HSR) project is new high speed rail construction from Seoul Suseo to Gyeonggi Pyeong-taek(61.1km). It is expected to solve railway congestion Gyeongbu line between Seoul and Si-heung and will expand HSR service that is concentrated in Seoul and Yongsan area to south-east part of Metropolitan area(Gang-nam, Gang-dong etc.), thus reducing regional travel time. It would be opened in December, 2016. KOTI surveyed Metropolitan Area HSR preference at Seoul, Yongsan, Gwangmyeon station, and Seoul express bus terminal and we questioned on 2,109 people to regional travel by KTX or express bus. In this study, We forecast changes in regional trip pattern from HSR and express bus users to Metropolitan Area HSR based on result of survey.

Kinetic Study of the Formation of Polypyrrole Nanoparticles in Water-Soluble Polymer/Metal Cation Systems: A Light-Scattering Analysis

Hong, Jin-Yong,Yoon, Hyeonseok,Jang, Jyongsik WILEY-VCH Verlag 2010 Small Vol.6 No.5

<P>A facile way to synthesize nanometer-sized polymer (polypyrrole, PPy) particles is explored on the basis of the formation of complexes between water-soluble polymers and metal cations in aqueous solution. The metal cation is used as an oxidizing agent to initiate the chemical oxidation polymerization of the corresponding monomer, and the water-soluble polymer effectively provides a steric stability for the growth of polymer nanoparticles during the polymerization process. Light-scattering analyses are performed to give insight into the behavior of the complexes in aqueous solution. In addition, major physical parameters affecting the formation of polymer nanoparticles are investigated, including hydrodynamic radius, radius of gyration, shape factor, and viscosity. By judicious control of these parameters, PPy nanoparticles with narrow size distribution can be readily fabricated in large quantities. It is also possible to control the diameter of the nanoparticles by changing critical synthetic variables. Importantly, PPy nanoparticles of ≈ 20–60 nm in diameter can be prepared without using any surfactants or specific templates; this novel strategy offers great possibility for mass production of polymer nanoparticles.</P> <B>Graphic Abstract</B> <P>A facile way to fabricate well-defined PPy nanoparticles in subkilogram quantities is demonstrated on the basis of the complexation of water-soluble polymer with metal cations. This novel strategy does not require an atypical temperature and pressure, and the simple process offers great possibility for mass production of polymer nanoparticles. <img src='wiley_img_2010/16136810-2010-6-5-SMLL200902231-content.gif' alt='wiley_img_2010/16136810-2010-6-5-SMLL200902231-content'> </P>

Communication—Screen-Printed Silver Electrodes for Enhanced Performance in Light-Emitting Devices Based on Electrochemiluminescence

Lee, Hyeonseok,Lee, Jong Ik,Park, Hee-Jin,Nam, Su-Yong,Kang, Moon Sung,Chun, Young Tea,Lee, Jiyoul The Electrochemical Society 2019 ECS journal of solid state science and technology Vol.8 No.11

<P>Electrochemiluminescence (ECL) based on a series of electrochemical processes of luminophores has attracted interests as a new light-emitting device platform referred to as the ECL device (ECLD). Here, we investigate the electrical and luminescence properties of ECLD with silver (Ag) electrodes. It is found that ECLD with screen-printed Ag electrodes prepared from carefully selected Ag paste ink could yield higher luminescence than that with thermally-evaporated Ag thin-film electrode. The results indicate that the low-cost large-areal printed ECLD potentially has comparable or surpassing performance to conventional vacuum-processed ECLDs.</P>