Article
Biochemistry & Molecular Biology
Siqi Shen, Gregory A. Davidson, Kun Yang, Zhihao Zhuang
Summary: The study used photoactivatable PCNA and Ub-PCNA probes to identify direct interactions of the Pol η catalytic core with both sides of the PCNA ring in the polymerase complex. This provides important insights for investigating PCNA-containing complexes involved in DNA replication, repair, and damage tolerance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Nathalia Varejao, Jara Lascorz, Joan Codina-Fabra, Gemma Belli, Helena Borras-Gas, Jordi Torres-Rosell, David Reverter
Summary: The post-translational modification of proteins by ubiquitin and ubiquitin-like modifiers, such as SUMO, plays a key role in protein homeostasis and DNA damage response. This study focuses on the complex structure of the SUMO E3 ligase Nse2 with an E2-SUMO thioester mimetic, revealing the essential role of two SIM-like motifs in restructuring upon binding the donor and E2-backside SUMO during the E3-dependent discharge reaction. Both SIM interfaces are crucial for the activity of Nse2, required for coping with DNA damage.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
George Yakoub, Yun-Seok Choi, Ronald P. Wong, Tina Strauch, Kezia J. Ann, Robert E. Cohen, Helle D. Ulrich
Summary: This study describes the design and application of avidity-based probes against the ubiquitylated forms of PCNA in budding yeast. These probes can be tuned to regulate PCNA ubiquitylation and can be used as biosensors or inhibitors. In live cells, they reveal the timing and site-specific sensitivity of PCNA ubiquitylation.
Article
Microbiology
Xu Feng, Baochang Zhang, Zhe Gao, Ruyi Xu, Xiaotong Liu, Sonoko Ishino, Mingxia Feng, Yulong Shen, Yoshizumi Ishino, Qunxin She
Summary: The study reveals that Sulfolobus islandicus Dpo2, previously predicted to be inactive, is actually a functional DNA polymerase involved in translesion synthesis. Dpo2 replicates undamaged DNA with high fidelity and efficiently extends mismatched and DNA lesion-containing substrates, highlighting its importance in DNA damage repair.
Article
Microbiology
Xu Feng, Baochang Zhang, Zhe Gao, Ruyi Xu, Xiaotong Liu, Sonoko Ishino, Mingxia Feng, Yulong Shen, Yoshizumi Ishino, Qunxin She
Summary: In this work, we discovered that Sulfolobus islandicus Dpo2, a B-family DNA polymerase once predicted to be inactive, is a functional DNA polymerase involved in translesion synthesis. S. islandicus Dpo2 belongs to a large group of B-family DNA polymerases (PolB2) that exists in many archaea and some bacteria, and they carry variations in conserved amino acids in the functional domains responsible for polymerization and proofreading. Contrary to predictions, this prokaryotic B-family DNA polymerase not only replicates undamaged DNA accurately, but also efficiently extends mismatched and DNA lesion-containing substrates. Based on our findings, we propose that this enzyme functions as an extender polymerase, representing the first prokaryotic enzyme of this type. Our data also suggests that this PolB2 enzyme serves as a functional counterpart of the eukaryotic DNA polymerase Pol zeta, which is dedicated to DNA damage repair.
Article
Biochemistry & Molecular Biology
Nicholas W. Ashton, Gabrielle J. Valles, Nancy Jaiswal, Irina Bezsonova, Roger Woodgate
Summary: USP7 is a critical deubiquitinating enzyme with important roles in multiple signaling pathways. The study reveals that DNA polymerase iota is a novel substrate of USP7, which requires binding to both TRAF and UBL1-2 domains for efficient deubiquitination. This discovery establishes a new bipartite mode of substrate binding for USP7.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Tomasz Czapik, Julita Piasecka, Ryszard Kierzek, Elzbieta Kierzek
Summary: The modified hammerhead ribozymes showed moderate cleavage activity and significantly inhibited the replication of influenza A virus. These findings suggest the potential therapeutic value of hammerhead ribozymes in fighting against influenza virus.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Multidisciplinary Sciences
Claudia Lancey, Muhammad Tehseen, Souvika Bakshi, Matthew Percival, Masateru Takahashi, Mohamed A. Sobhy, Vlad S. Raducanu, Kerry Blair, Frederick W. Muskett, Timothy J. Ragan, Ramon Crehuet, Samir M. Hamdan, Alfredo De Biasio
Summary: Research shows that Pol kappa can replicate damaged DNA templates by interacting with PCNA. When the internal PIP-box interaction is lost, Pol kappa can be retained on DNA through a secondary interaction with PCNA mono-ubiquitylation.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Kaitlyn Waters, Hamilton J. Wan, Lei Han, Jianli Xue, Matthew Ykema, Yizhi J. Tao, Xiu-Feng Wan
Summary: The research revealed that the polymerase activities of PB1 are influenced not only by residues within conserved motifs, but also by residues across inter-motif regions, primarily located at the base of the palm domain. Mutations outside the PB1 conserved motifs may impact RNA replication and host adaptation of influenza virus.
Article
Biochemistry & Molecular Biology
Davi Jardim Martins, Jenny Kaur Singh, Tiya Jahjah, Alexandre Teixeira Vessoni, Giovana da Silva Leandro, Matheus Molina Silva, Denis Serge Francois Biard, Annabel Quinet, Carlos Frederico Martins Menck
Summary: Xeroderma pigmentosum (XP) variant cells deficient in Polη polymerase show increased sensitivity to UV radiation, affecting cell proliferation and migration. Polι may act as a backup for Polη in bypassing UV-induced photoproducts.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra Vaisman, John P. McDonald, Mallory R. Smith, Sender L. Aspelund, Thomas C. Evans, Roger Woodgate
Summary: Y-family DNA polymerases consist of six phylogenetically separate subfamilies, with representatives found in all three domains of life. Different evolutionary diversity exists within eukaryotes, with different species possessing varying numbers and types of Y-family pols. The Y-family pols from Thermomyces lanuginosus show increased thermostability and share major biochemical properties with their human counterparts, displaying low fidelity during DNA synthesis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Virology
Paula Michalak, Julita Piasecka, Barbara Szutkowska, Ryszard Kierzek, Ewa Biala, Walter N. Moss, Elzbieta Kierzek
Summary: The functionality of RNA is dependent on its structure, with some structural motifs conserved among different strains of IAV. High-throughput methods combined with in vitro experimental data can aid in the interpretation and optimization of RNA structures for potential targeting approaches.
Article
Chemistry, Medicinal
Priya Bhutani, Makay T. Murray, Craig W. Sommer, Katie A. Wilson, Stacey D. Wetmore
Summary: The study investigated the impact of the size and flexibility of O4-POB-T on pol eta replication outcomes, revealing that while O4-POB-T forms favorable structures in the pol eta active site and DNA duplexes, its inherent dynamic nature periodically disrupts hydrogen bonding, affecting dGTP insertion and stabilization of damaged DNA. This sheds light on the nonmutagenic replication pathway for thymine alkylated lesions by pol eta and emphasizes the broader implications of bulky moiety size, flexibility, and position on mutagenic outcomes.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Haruhiko Ehara, Tomoya Kujirai, Mikako Shirouzu, Hitoshi Kurumizaka, Shun-ichi Sekine
Summary: This study used cryo-electron microscopy to obtain structures of RNA polymerase II (RNAPII) passing through nucleosomes during gene transcription. The researchers also identified the roles of transcription elongation factors and histone chaperones in nucleosome disassembly and reassembly.
Article
Multidisciplinary Sciences
Vadim Molodtsov, Chengyuan Wang, Emre Firlar, Jason T. T. Kaelber, Richard H. H. Ebright
Summary: This study reports the preparation and cryogenic electron microscopy structures of functional complexes involved in factor-dependent transcription termination from a ring-shaped hexameric ATP-dependent molecular motor called Rho. The structures reveal the mechanism of Rho-mediated transcription termination and its interaction with other factors. This research has significant implications in understanding the function of Rho in transcription and translation coupling.
Article
Biochemistry & Molecular Biology
Nina T. Odermatt, Moreno Lelli, Torsten Herrmann, Luciano A. Abriata, Aleksandre Japaridze, Hubert Voilquin, Rajkumar Singh, Jeremie Piton, Lyndon Emsley, Giovanni Dietler, Stewart T. Cole
JOURNAL OF STRUCTURAL BIOLOGY
(2020)
Article
Biochemical Research Methods
Jae Bem You, Byungjin Lee, Yunho Choi, Chang-Soo Lee, Matthias Peter, Sung Gap Im, Sung Sik Lee
Correction
Cell Biology
Antoni G. Wrobel, Zuzana Kadlecova, Jan Kamenicky, Ji-Chun Yang, Torsten Herrmann, Bernard T. Kelly, Airlie J. McCoy, Philip R. Evans, Stephen Martin, Stefan Mueller, Susanne Salomon, Filip Sroubek, David Neuhaus, Stefan Honing, David J. Owen
DEVELOPMENTAL CELL
(2020)
Article
Multidisciplinary Sciences
Kim Krighaar Rasmussen, Andres Palencia, Anders K. Varming, Habiba El-Wali, Elisabetta Boeri Erba, Martin Blackledge, Karin Hammer, Torsten Herrmann, Mogens Kilstrup, Leila Lo Leggio, Malene Ringkjobing Jensen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Biochemistry & Molecular Biology
Ewa Blaszczak, Natalia Lazarewicz, Aswani Sudevan, Robert Wysocki, Gwenael Rabut
Summary: Protein-protein interactions play a crucial role in biological processes and are attractive drug targets for various human diseases. PCAs offer a direct and versatile approach to study PPIs, enabling the detection of interactions in their native cellular environment. They are valuable tools for large-scale experiments exploring PPI networks and drug screening.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemical Research Methods
Marc Melkonian, Camille Juigne, Olivier Dameron, Gwenael Rabut, Emmanuelle Becker
Summary: This study investigates the issue of redundancy in protein-protein interaction databases and proposes a method using Semantic Web technologies to detect and eliminate redundancy. They find that implicit redundancy has a significant impact on the results and suggest excluding it when calculating confidence-related metrics.
Article
Biochemistry & Molecular Biology
Arun T. John Peter, Sabine N. S. van Schie, Ngaam J. Cheung, Agnes H. Michel, Matthias Peter, Benoit Kornmann
Summary: The membrane lipid composition of eukaryotic cells varies among different organelles. This study focuses on simplifying and reorganizing yeast phospholipid synthesis by redirecting synthesis reactions to specific subcellular locations. Through genetic screening, genes involved in lipid homeostasis, metabolism, and transport were identified, with a particular focus on the requirement for Csf1 in interorganelle lipid transport and homeostatic adaptation.
Article
Biochemistry & Molecular Biology
Weaam Mohamed, Sophia L. Park, Julius Rabl, Alexander Leitner, Daniel Boehringer, Matthias Peter
Summary: The human GID (hGID) complex utilizes two distinct modules, WDR26 and GID4, for substrate recruitment and ubiquitination. GID4 functions as an adaptor for some substrates while WDR26 and Gid7 utilize different binding sites. The study also reveals the regulation of GID4 substrate binding and ligase activity by ARMC8 alpha.
Article
Biochemistry & Molecular Biology
Anne Schreiber, Ben C. Collins, Colin Davis, Radoslav Enchev, Angie Sedra, Rocco D'Antuono, Ruedi Aebersold, Matthias Peter
Summary: This study elucidates the critical role of Atg1 in autophagy, demonstrating how it is activated by Atg8-PE to phosphorylate substrates on the autophagosomal membrane and regulate autophagosome formation. The research also reveals the molecular mechanisms of positive and negative feedback by Atg1 and the spatiotemporal regulation of autophagy through phosphorylation events.
Review
Biochemistry & Molecular Biology
Ranjan Mishra, Nicolas Minc, Matthias Peter
Summary: This article reviews the types and origins of mechanical forces experienced by unicellular yeast, as well as how these forces affect cell polarity and the invasion mechanism of pathogenic fungi. Additionally, the article discusses the common force-sensing mechanisms and downstream mechanotransduction mechanisms.
TRENDS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Vera M. Kissling, Giordano Reginato, Eliana Bianco, Kristina Kasaciunaite, Janny Tilma, Gea Cereghetti, Natalie Schindler, Sung Sik Lee, Raphael Guerois, Brian Luke, Ralf Seidel, Petr Cejka, Matthias Peter
Summary: This study reveals the oligomerization mechanism of the Mre11-Rad50 complex and its functional significance in DNA damage repair. The results show that Rad50 mediates the oligomerization of the Mre11-Rad50 complex, and its mutations may be linked to hereditary cancer predisposition.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Patrik Simmler, Cedric Cortijo, Lisa Maria Koch, Patricia Galliker, Silvia Angori, Hella Anna Bolck, Christina Mueller, Ana Vukolic, Peter Mirtschink, Yann Christinat, Natalie R. Davidson, Kjong-Van Lehmann, Giovanni Pellegrini, Chantal Pauli, Daniela Lenggenhager, Ilaria Guccini, Till Ringel, Christian Hirt, Kim Fabiano Marquart, Moritz Schaefer, Gunnar Ratsch, Matthias Peter, Holger Moch, Markus Stoffel, Gerald Schwank
Summary: Mutations in the splicing factor SF3B1 are frequently occurring in various cancers and drive tumor progression. This study demonstrates that SF3B1 is a target gene of HIF1 and positively regulates HIF1 pathway activity by facilitating the binding of HIF1 complex to HREs. The reduction in SF3B1 levels impede tumor formation and progression via impaired HIF signaling in a mouse model for pancreatic cancer.
Article
Biochemistry & Molecular Biology
Federico Uliana, Rodolfo Ciuffa, Ranjan Mishra, Andrea Fossati, Fabian Frommelt, Sabrina Keller, Martin Mehnert, Eivind Salmorin Birkeland, Frank van Drogen, Nevena Srejic, Matthias Peter, Nicolas Tapon, Ruedi Aebersold, Matthias Gstaiger
Summary: This article describes an experimental strategy to investigate the interdependencies between protein phosphorylation and Protein-Protein Interactions (PPIs). The strategy involves systematically mapping the phosphorylation landscape of a target protein, assigning different proteoforms of the target protein to distinct protein complexes, and analyzing them in cells lacking regulators of the target protein. The study applied this strategy to YAP1 and identified multiple YAP1 phosphosites associated with distinct complexes, providing insights into their regulation by Hippo pathway members.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Maximilian Mosbacher, Sung Sik Lee, Gilad Yaakov, Mariona Nadal-Ribelles, Eulalia de Nadal, Frank van Drogen, Francesc Posas, Matthias Peter, Manfred Claassen
Summary: This study characterizes the regulation of MAP kinase Hog1 in Saccharomyces cerevisiae and reveals a mixed phosphorylation mechanism regulated by a positive feedback loop. Simulations show that this mechanism is necessary for full sensitivity to stimuli and robustness to perturbations.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Anna Stier, Samuel Gilberto, Weaam Mohamed, Lars N. Royall, Jonne Helenius, Ivan Mikicic, Tatjana Sajic, Petra Beli, Daniel J. Mueller, Sebastian Jessberger, Matthias Peter
Summary: CUL4A and CUL4B are paralogs that assemble cullin-RING E3 ubiquitin ligase (CRL) complexes regulating chromatin-associated cellular functions. The unique N-terminal extension of CUL4B is heavily phosphorylated during mitosis, and this phosphorylation is disrupted in the CUL4B-P50L mutation causing X-linked intellectual disability (XLID). Phenotypic characterization and mutational analysis showed that CUL4B phosphorylation is essential for mitosis progression and controls spindle positioning and cortical tension.