Article
Multidisciplinary Sciences
Jingpeng Zhu, Yina Gao, Yong Wang, Qi Zhan, Han Feng, Xiu Luo, Peipei Li, Songqing Liu, Hai Hou, Pu Gao
Summary: This study reports on the detailed structure and molecular mechanisms of a non-canonical type I R-M methyltransferase, providing insights into the mechanisms of m6A/m4C catalysis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Ashkan Karimi, Kaixiang Wang, Kaleena Basran, William Copp, Nathan W. Luedtke
Summary: A new fluorescent cytosine analog, C-ts, was synthesized and incorporated into hemiprotonated base pairs that form i-motif structures. Unlike previous fluorescent base analogs, C-ts mimics the acid-base properties of cytosine while exhibiting bright and red-shifted fluorescence upon protonation. Ratiometric analysis of C-ts emission wavelengths allows real-time tracking of structural conversions between different DNA structures. Results suggest that hemiprotonated C+:C base pairs can form in partially folded single-stranded DNA in the absence of global i-motif structures.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Oncology
Anthony B. B. El-Khoueiry, James Clarke, Tobias Neff, Tim Crossman, Nirav Ratia, Chetan Rathi, Paul Noto, Aarti Tarkar, Ignacio Garrido-Laguna, Emiliano Calvo, Jordi Rodon, Ben Tran, Peter J. J. O'Dwyer, Adam Cuker, Albiruni R. Abdul R. Razak
Summary: GSK3368715, a reversible inhibitor of type I protein methyltransferases, showed anticancer activity in preclinical studies. This Phase 1 study evaluated its safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with advanced solid tumors. However, due to a higher-than-expected incidence of thromboembolic events, the study was terminated.
BRITISH JOURNAL OF CANCER
(2023)
Article
Immunology
Zheng-jun Gao, Wen-ping Li, Xin-tao Mao, Tao Huang, Hao-li Wang, Yi-ning Li, Bao-qin Liu, Jiang-yan Zhong, Chai Renjie, Jin Jin, Yi-yuan Li
Summary: This study reveals that deficiency of Uhrf1 in myeloid cells significantly upregulates Ifnb expression, enhancing resistance to viral infection. Whole-genome bisulfite sequencing identified a single nucleotide methylation site in the Ifnb promoter region that disrupts IRF3 recruitment. Further experiments confirmed the critical role of this methylated site in regulating Ifnb expression and antiviral responses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Luiz F. M. Passalacqua, Michael T. Banco, Jared D. Moon, Xing Li, Samie R. Jaffrey, Adrian R. Ferre-D'Amare
Summary: Research has found that a DNA molecule can form complex three-dimensional structures without the involvement of proteins or RNA. This structure is more compact than many comparable RNA structures, suggesting new principles of nucleic acid organization.
Article
Biochemistry & Molecular Biology
Marianna Martella, Flavia Pichiorri, Rupesh Chikhale, Mahmoud A. S. Abdelhamid, Zoe A. E. Waller, Steven S. Smith
Summary: Concatemers of d(TCCC) are found throughout the human genome and can cause deletions at the RACK7 locus. They form G-quadruplexes for d(GGGA)(n) sequences with n > 3, and i-motif structures for d(TCCC)(n) sequences at neutral pH with n >= 7. Deletions in the PC3 cell line only occur when the d(TCCC)(n) variant forms unresolved i-motif structures at neutral pH.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Yoshihiro Sohtome, Tadahiro Shimazu, Yoichi Shinkai, Mikiko Sodeoka
Summary: Developing synthetic strategies to construct covalent bonds is a common research topic among synthetic chemists. The success of such strategies relies on the tunability of conditions such as catalysts, reagents, solvents, and reaction temperature. However, controlling chemical reactions in living cells poses challenges due to a smaller number of hit substrates and a complex and inflexible environment. The use of chemical methylome analysis serves as an example of bridging the gap between chemistry and biology in this context.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Pil-Won Seo, Andreas Hofmann, Jun-Ha Kim, Seung-A Hwangbo, Jun-Hong Kim, Ji-Won Kim, Thi Yen Ly Huynh, Hyon E. Choy, Soo-Jung Kim, Jimin Lee, Jie-Oh Lee, Kyeong Sik Jin, Suk-Youl Park, Jeong-Sun Kim
Summary: Type I restriction-modification enzymes are composed of methylation, DNA sequence-recognition, and restriction subunits. In this study, the crystal structure of the intact MTase from Vibrio vulnificus YJ016 in complex with DNA-mimicking Ocr protein and SAH was determined. The reconstructed structure of the MTase dimer revealed its symmetry and conformational flexibility in recognizing DNA regions. This study provides insights into the structural characteristics of Type I restriction-modification enzymes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Microbiology
Zhihao Wang, Hongliang Wang, Nancy Mulvenna, Maximo Sanz-Hernandez, Peipei Zhang, Yanqing Li, Jia Ma, Yawen Wang, Steve Matthews, Sivaramesh Wigneshweraraj, Bing Liu
Summary: Proteins mimic DNA to occupy DNA binding sites, preventing further access. The phage protein Gp44 employs this strategy to inhibit host RNA polymerase, leading to bacterial growth inhibition. This non-specific strategy may have potential applications in developing genetically engineered phages for phage therapy targeting a range of bacterial hosts.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yusuke Kuramochi, Ren Sato, Hiroki Sakuma, Akiharu Satake
Summary: By coordinating aldehyde derivatives to Zn porphyrins, a stable porphyrin dimer structure is obtained, which exhibits good catalytic activity and durability in photocatalytic CO2 reduction.
Review
Microbiology
Qun Gao, Shuwei Lu, Yuwei Wang, Longgui He, Mingshu Wang, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Sai Mao, Xumin Ou, Di Sun, Bin Tian, Anchun Cheng
Summary: Epigenetics regulates expression levels of important genes in both prokaryotes and eukaryotes without changing genetic DNA sequences. DNA methylation is a universal epigenetic mechanism in all organisms. In bacteria, DNA methylation is the main form of epigenetic regulation and plays important roles in clinically relevant phenotypes. This review focuses on recent developments in understanding bacterial DNA methyltransferases and their involvement in gene expression regulation, DNA replication, and repair control. The advancements in sequencing techniques have allowed for the characterization of genome-wide epigenetic regulation, which may lead to the development of novel epigenetic inhibitors for biomedical applications.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ashleigh Shannon, Bhawna Sama, Pierre Gauffre, Theo Guez, Francoise Debart, Jean-Jacques Vasseur, Etienne Decroly, Bruno Canard, Francois Ferron
Summary: In this study, we discovered that the ORF1a region of certain members of the large genome Tobaniviridae family indeed harbors N7-specific methyltransferase activity. We presented its structure as the first N7-specific Rossmann-fold (RF) methyltransferase identified for (+)RNA viruses, which is remarkably different from that of the known Coronaviridae ORF1b N7-MTase gene. The appearance of this methyltransferase in an unexpected location in the genome introduces a split-off in the classification of Tobaniviridae.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Alexandra Mack, Max Emperle, Philipp Schnee, Sabrina Adam, Juergen Pleiss, Pavel Bashtrykov, Albert Jeltsch
Summary: Somatic R882H DNMT3A mutations are common in AML, but their pathogenic mechanism is unclear. R882H mutations affect the sequence preferences of DNMT3A and have a dominant effect on its catalytic properties in samples containing WT and R882H subunits.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Retzer, Jeanette Moulinier-Anzola, Rebecca Lugsteiner, Nataliia Konstantinova, Maximilian Schwihla, Barbara Korbei, Christian Luschnig
Summary: Intracellular sorting and abundance of plasma membrane proteins are crucial for plants to sense and respond to environmental inputs. The reversible covalent modification by ubiquitin plays a key role in inducing adjustments in protein localization and functionality. The RING DOMAIN LIGASE family, including RGLG1, has been implicated in endocytic vacuolar cargo sorting, and this study provides evidence for their role in cargo trafficking between plasma membrane and endosomal compartments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Pierre Aldag, Marius Rutkauskas, Julene Madariaga-Marcos, Inga Songailiene, Tomas Sinkunas, Felix Kemmerich, Dominik Kauert, Virginijus Siksnys, Ralf Seidel
Summary: The authors dissect the target search and recognition process of the Type I CRISPR-Cas complex Cascade by monitoring DNA binding and R-loop formation. They quantify the effect of DNA supercoiling on target recognition and demonstrate the use of facilitated diffusion in target search. The findings highlight the importance of considering DNA supercoiling and limited 1D diffusion in understanding CRISPR-Cas target recognition and search.
NATURE COMMUNICATIONS
(2023)
