류은진 교수
Ryu, Eunjin
서울대학교 · 생화학·유전·분자생물학
연구실 소개
류은진 교수의 연구실은 주로 금속 촉매를 활용한 C-H 결합 기반의 고도로 선택적인 유기합성 반응, 특히 산화적 재결합을 통한 C-C 결합 형성 메커니즘을 중심으로 연구를 진행하고 있습니다. 또한 DNA 복제 과정에서 발생하는 복제 포일 스탑과 관련된 유전자 조절 메커니즘, 특히 PCNA의 유비퀴틴화 조절과 ELG1, USP1-UAF1 복합체의 역할을 규명하며 유전자 안정성 유지 메커니즘을 탐구하고 있습니다. 이는 암 발생과 관련된 유전자 손상 복구 및 세포 주기 조절의 분자 기전을 이해하는 데 기여하고 있습니다.
연구 현황
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주요 논문
15An iridium-catalyzed direct C-H amidation of weakly coordinating substrates, in particular of those bearing ester and ketone groups, under very mild conditions has been developed. The observed high reaction efficiency was achieved by the combined use of acetic acid and lithium carbonate as additives.
Temporal and spatial regulation of the replication factory is important for efficient DNA replication. However, the underlying molecular mechanisms are not well understood. Here, we report that ATAD5 regulates the lifespan of replication factories. Reduced expression of ATAD5 extended the lifespan of replication factories by retaining proliferating cell nuclear antigen (PCNA) and other replisome proteins on the chromatin during and even after DNA synthesis. This led to an increase of inactive re
The level of monoubiquitinated proliferating cell nuclear antigen (PCNA) is closely linked with DNA damage bypass to protect cells from a high level of mutagenesis. However, it remains unclear how the level of monoubiquitinated PCNA is regulated. Here, we demonstrate that human ELG1 protein, which comprises an alternative replication factor C (RFC) complex and plays an important role in preserving genomic stability, as an interacting partner for the USP1 (ubiquitin-specific protease 1)-UAF1 (USP
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 cat
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 cat
Direct conversion of C-H bonds into C-C bonds is a promising alternative to the conventional cross-coupling reactions, thus giving rise to a wide range of efficient catalytic C-H functionalization reactions. Among the elementary stages in the catalytic C-C bond formation, reductive elimination constitutes a key step of the catalytic cycle, and, therefore, extensive studies have been made to facilitate this process. In this regard, oxidation on the metal center of a post-transmetalation intermedi
R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflict (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX
A single molecular rhodium catalyst system (PC2-Cp<sup>#</sup>Rh<sup>III</sup>) bearing two functional domains for both photosensitization and C-H carbometalation was designed to enable an intramolecular redox process. The hypothesized charge-transfer species (PC2<sup>•-</sup>-Cp<sup>#</sup>Rh<sup>IV</sup>) was characterized by spectroscopic and electrochemical analyses. This photoinduced internal oxidation allows a facile access to the triplet state of the key post-transmetalation intermediate
Abstract An iridium‐catalyzed direct CH amidation of weakly coordinating substrates, in particular of those bearing ester and ketone groups, under very mild conditions has been developed. The observed high reaction efficiency was achieved by the combined use of acetic acid and lithium carbonate as additives.
Eukaryotic sliding clamp proliferating cell nuclear antigen (PCNA) plays a critical role as a processivity factor for DNA polymerases and as a binding and acting platform for many proteins. The ring-shaped PCNA homotrimer and the DNA damage checkpoint clamp 9-1-1 are loaded onto DNA by clamp loaders. PCNA can be loaded by the pentameric replication factor C (RFC) complex and the CTF18-RFC-like complex (RLC) in vitro. In cells, each complex loads PCNA for different purposes; RFC-loaded PCNA is es
Regioselective C-H functionalization on quinolines is of high interest to lead to value-added products. Herein, we describe the development of Ru-catalyzed deoxygenative regioselective C8 arylation of quinoline <i>N</i>-oxides with arylboronic esters. Mechanistic studies revealed that it proceeds in a tandem process of arylation and then deoxygenation, wherein both steps were found to be catalytic with the ruthenium species.
Human rhinoviruses (hRVs) are the main causative pathogen for common colds and are associated with the exacerbation of asthma. The wide variety in hRV serotypes has complicated the development of rhinovirus replication inhibitors. In the current investigation, we developed a novel series of benzothiophene derivatives and their analogues (6-8) that potently inhibit the replication of both hRV-A and hRV-B strains. Compound 6g inhibited the replication of hRV-B14, A21, and A71, with respective EC<s
Reactive oxygen species (ROS) generate oxidized bases and single-strand breaks (SSBs), which are fixed by base excision repair (BER) and SSB repair (SSBR), respectively. Although excision and repair of damaged bases have been extensively studied, the function of the sliding clamp, proliferating cell nuclear antigen (PCNA), including loading/unloading, remains unclear. We report that, in addition to PCNA loading by replication factor complex C (RFC), timely PCNA unloading by the ATPase family AAA
The human rhinovirus (hRV) is the causative agent of the common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. The high rate of mutations and variety of serotypes are limiting the development of anti-hRV drugs, which emphasizes the need for the discovery of novel lead compounds. Previously, we identified antiviral compound <b>1</b> that we used here as the starting material for developing a novel compound series with high ef
Herein, we describe the mechanistic details on the oxidatively induced reductive elimination of isolated methyl iridium and ruthenium metallacycle complexes. It was demonstrated that the otherwise challenging C─C bond formation is indeed facilitated by external oxidation, being enabled under mild conditions. Computational analyses supported the proposed high‐valent pathway, where the energy barrier for reductive elimination significantly decreases upon the metallic oxidation to facilitate the de
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