Hanyang University · 生化学・遺伝学・分子生物学
Professor Sang-Hun Lee's research lab focuses on molecular mechanisms underlying DNA replication and genome stability, with a particular emphasis on the roles of key replication factors such as Activator 1 (A1), PCNA, and DNA polymerases δ and ε. The lab also investigates the pathogenic mechanisms of neurodegenerative diseases, especially Parkinson’s disease, using human stem cell-derived models to study genetic mutations (e.g., in *DNAJC6*) and their impact on neuronal function, protein aggregation, and organelle homeostasis. Additionally, the lab explores the role of cellular metabolites, such as vitamin C, in epigenetic regulation and neural differentiation, particularly toward midbrain dopamine neurons. These interdisciplinary studies integrate molecular biology, stem cell technology, and disease modeling to uncover fundamental biological processes and therapeutic targets.
Figures are computed from collected data and may differ slightly.
Activator 1 (A1) is a multiprotein complex which is essential for proliferating cell nuclear antigen (PCNA)-dependent DNA polymerase delta (pol delta) activity and efficient in vitro DNA synthesis in the SV40 dipolymerase replication system. In this report, we describe the isolation of A1 from HeLa cytosolic extracts. A1 stimulated pol delta activity in singly primed phi X174 DNA or (dA)4500.oligo(dT)12-18 in reactions containing PCNA, single-stranded DNA binding protein (SSB), and ATP. Using th
The isolation of DNA polymerase (Pol) epsilon from extracts of HeLa cells is described. The final fractions contained two major subunits of 210 and 50 kDa which cosedimented with Pol epsilon activity, similar to those described previously (Syvaoja, J., and Linn, S. (1989) J. Biol. Chem. 264, 2489-2497). The properties of the human Pol epsilon and the yeast Pol epsilon were compared. Both enzymes elongated singly primed single-stranded circular DNA templates. Yeast Pol epsilon required the presen
In the presence of a single-stranded-DNA-binding protein (SSB), the elongation of primed DNA templates by DNA polymerase delta (pol delta) is dependent on ATP and two protein factors, activator 1 (A1) and proliferating cell nuclear antigen (PCNA). We have examined the interaction of these proteins with (dA)4500.(dT)12-18 by measuring their ability to form stable complexes with this DNA. In the presence of ATP, A1, PCNA, and pol delta formed a stable complex with DNA that could be isolated by gel
Loss-of-function mutations of <i>DNAJC6</i>, encoding HSP40 auxilin, have recently been identified in patients with early-onset Parkinson's disease (PD). To study the roles of DNAJC6 in PD pathogenesis, we used human embryonic stem cells with CRISPR-Cas9-mediated gene editing. Here, we show that <i>DNAJC6</i> mutations cause key PD pathologic features, i.e., midbrain-type dopamine (mDA) neuron degeneration, pathologic α-synuclein aggregation, increase of intrinsic neuronal firing frequency, and
The origin and functional specialization of dermal macrophages in cutaneous infections have been little studied. In this paper, we show that a strain of <i>Leishmania major</i> (<i>L. major</i> Seidman [LmSd]) that produces nonhealing cutaneous lesions in conventionally resistant C57BL/6 mice was more efficiently taken up by M2-polarized bone marrow (BM)-derived macrophages (BMDMs) in vitro and by mannose receptor (MR)<sup>hi</sup> dermal macrophages in vivo compared with a healing strain (<i>L.
Intracellular Vitamin C (VC) is maintained at high levels in the developing brain by the activity of sodium-dependent VC transporter 2 (Svct2), suggesting specific VC functions in brain development. A role of VC as a cofactor for Fe(II)-2-oxoglutarate-dependent dioxygenases has recently been suggested. We show that VC supplementation in neural stem cell cultures derived from embryonic midbrains greatly enhanced differentiation toward midbrain-type dopamine (mDA) neurons, the neuronal subtype ass
Water transport across root systems of young cucumber (Cucumis sativus L.) seedlings was measured following exposure to low temperature (LT, 8-13 degrees C) for varying periods of time. In addition, the amount of water transported through the stems was evaluated using a heat-balance sap-flow gauge. Following LT treatment, hydrogen peroxide was localized cytochemically in root tissue by the oxidation of cerium (III) chloride. The effects of hydrogen peroxide on the hydraulic conductivity of singl
Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient i
Neural precursor (NP) cells from adult mammalian brains can be isolated, expanded in vitro, and potentially used as cell replacement source material for treatment of intractable brain disorders. Reduced ethical concerns, lack of teratoma formation, and possible ex vivo autologous transplantation are critical advantages to using adult NP donor cells over cells from fetal brain tissue or embryonic stem cells. However, the usage of adult NP cells is limited by the ability to induce specific neuroch
This study suggests that coadministration of P. ginseng and warfarin in ischemic stroke patients does not influence the pharmacologic action of warfarin.
The thalamic reticular nucleus (TRN) provides inhibitory innervation to most thalamic relay nuclei and receives excitatory innervation from both cortical and thalamic neurons. Ultimately, information transfer through the thalamus to the neocortex is strongly influenced by TRN. In addition, the reciprocal synaptic connectivity between TRN with associated thalamic relay nuclei is critical in generating intrathalamic rhythmic activities that occur during certain arousal states and pathophysiologica
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