Article
Biochemistry & Molecular Biology
Paul Villain, Violette da Cunha, Etienne Villain, Patrick Forterre, Jacques Oberto, Ryan Catchpole, Tamara Basta
Summary: Research shows that expressing bacterial gyrase from Thermotoga maritima in the archaeon Thermococcus kodakarensis can induce negative supercoiling and impact gene expression and chromosomal topology. However, this artificially introduced supercoiling activity did not significantly affect the growth rate of the archaeon.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Miriam Garcia-Lopez, Diego Megias, Maria-Jose Ferrandiz, Adela G. de la Campa
Summary: Two enzymes, gyrase and topoisomerase I, play important roles in maintaining supercoiling in Streptococcus pneumoniae. The ratio of these enzymes affects supercoiling and cell viability, suggesting a potential mechanism for the action of topoisomerase-targeting antibiotics.
FRONTIERS IN MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ian G. Cowell, John W. Casement, Caroline A. Austin
Summary: Transcription and its regulation are affected by DNA torsion and supercoiling, which are resolved by DNA topoisomerases. This review focuses on one type of DNA topoisomerase II beta, which plays a critical role in developmental transcription and signal-induced transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonio A. A. de Vasconcelos Junior, Jose M. Tirado-Velez, Antonio J. Martin-Galiano, Diego Megias, Maria-Jose Ferrandiz, Pablo Hernandez, Monica Amblar, Adela G. de la Campa
Summary: In this study, a new topoisomerase I regulator protein (StaR) was characterized in Streptococcus pneumoniae. It was found that StaR directly affects novobiocin susceptibility and needs to be maintained within a narrow range.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Suchintak Dash, Cristina S. D. Palma, Ines S. C. Baptista, Bilena L. B. Almeida, Mohamed N. M. Bahrudeen, Vatsala Chauhan, Rahul Jagadeesan, Andre S. Ribeiro
Summary: The study investigated the underlying mechanisms of Escherichia coli cold shock response. It was found that some cold shock repressed genes could be triggered by changes in DNA supercoiling. Additionally, the response strengths to cold shock and gyrase inhibition were correlated, and cold shock led to an increase in nucleoid density and a decrease in cellular energy.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Vita Vidmar, Marlene Vayssieres, Valerie Lamour
Summary: DNA topoisomerases play a crucial role in resolving topological problems in DNA. They can recognize DNA topology and catalyze various reactions by cutting and rejoining DNA. While the mechanisms of DNA cleavage and re-ligation have been extensively studied, the structural rearrangements required for DNA-gate opening and strand transfer, especially in type IA topoisomerases, remain unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yair A. G. Fosado, Davide Michieletto, Chris A. Brackley, Davide Marenduzzo
Summary: The study investigates the effect of transcription on DNA supercoiling kinetics, revealing the formation of writhe structures at a distance from the transcribing RNA polymerase. Additionally, it shows that positive supercoils generated by RNAP can destabilize nucleosomes long before the transcriptional machinery reaches the histone octamer. The research also analyzes the relaxation dynamics of supercoiled DNA, highlighting the significantly different timescales of twist diffusion and writhe relaxation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Physics, Multidisciplinary
Purba Chatterjee, Nigel Goldenfeld, Sangjin Kim
Summary: Recent experiments have shown that mechanical stress associated with transcription can lead to a transition in RNA polymerase group dynamics from cooperative to antagonistic upon promoter repression. A continuum deterministic model for transcription under torsion was developed to elucidate the mechanism behind this transition, successfully reproducing experimental findings and shedding light on the interplay of mechanical and biological factors in the collective dynamics of molecular machines involved in gene expression.
PHYSICAL REVIEW LETTERS
(2021)
Article
Mathematical & Computational Biology
Xiyan Yang, Zihao Wang, Yahao Wu, Tianshou Zhou, Jiajun Zhang
Summary: This article investigates the influence of the promoter cycle model on transcriptional bursting kinetics, and proposes that multiple ON mechanisms can lead to bimodal burst-size distribution, antagonistic timing of ON and OFF, and diverse burst frequencies, further contributing to cell-to-cell variability in the mRNA expression level.
MATHEMATICAL BIOSCIENCES AND ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Agnieszka Strzalka, Agnieszka Kois-Ostrowska, Magda Kedra, Tomasz Lebkowski, Grazyna Bieniarz, Marcin J. Szafran, Dagmara Jakimowicz
Summary: Bacterial chromosome topology is regulated by topoisomerases and nucleoid-associated proteins. Streptomyces bacteria utilize the topoisomerase I (TopA) and the HU homologue HupA to maintain chromosome organization and distribution, which is essential for hyphal growth and production of clinically important compounds.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Laura Martin, Maria Victoria Neguembor, Maria Pia Cosma
Summary: One of the biggest paradoxes in biology is the disparity in size between the human genome and the nucleus that contains it. Despite being approximately 2 meters long, the DNA must be compacted and accessible for replication and transcription. The role of DNA torsional stress as a regulator of chromatin compaction and accessibility is discussed, with a focus on the influence of topoisomerases on genome organization.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alexandre Duprey, Eduardo A. Groisman
Summary: DNA supercoiling is a crucial factor in controlling cellular processes, with similarities and differences across different domains of life. Topoisomerases play a key role in mediating changes in DNA supercoiling.
Article
Biochemistry & Molecular Biology
Shubham Tripathi, Sumitabha Brahmachari, Jose N. Onuchic, Herbert Levine
Summary: Multiple RNA polymerases (RNAPs) transcribing a gene can exhibit collective behavior, where the transcription elongation rate increases with the rate of transcription initiation. Recent studies suggest that even RNAPs separated by long distances can cooperate by modifying the DNA segment under transcription. This theoretical model incorporates the mechanical coupling between RNAP translocation and DNA torsional response, and stochastic simulations demonstrate DNA supercoiling-mediated long-range cooperation between co-transcribing RNAPs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Monica S. Guo, Ryo Kawamura, Megan L. Littlehale, John F. Marko, Michael T. Laub
Summary: The GapR-seq method allows high-resolution mapping of positive supercoiling in genomes, revealing its widespread presence, association with transcription, and enrichment between certain genes. This approach provides new insights into chromosome structure and organization that are not accessible with existing methods like Hi-C.
Article
Computer Science, Artificial Intelligence
Theotime Grohens, Sam Meyer, Guillaume Beslon
Summary: DNA supercoiling is an ancestral regulation mechanism of gene expression in bacteria. This study explores the coupled dynamics of DNA supercoiling and transcription at the genome scale and demonstrates that changes in global DNA supercoiling can trigger differentiated responses in gene expression levels, serving as the basis for the evolution of specialized phenotypes.
Article
Biochemistry & Molecular Biology
Veronika te Boekhorst, Liying Jiang, Marius Mahlen, Maaike Meerlo, Gina Dunkel, Franziska C. Durst, Yanjun Yang, Herbert Levine, Boudewijn M. T. Burgering, Peter Friedl
Summary: This article studies the molecular mechanisms of cancer cell invasion and metastasis under hypoxic conditions and identifies calpain-2 as a key regulator of the transition from collective to amoeboid dissemination in breast and head and neck carcinoma cells. The study reveals that hypoxia induces calpain-2-mediated amoeboid conversion by deactivating beta 1 integrins. Targeted intervention of calpain-2 activity can restore normal cell phenotype and prevent lung metastasis.
Article
Biochemistry & Molecular Biology
Shubham Tripathi, Sumitabha Brahmachari, Jose N. Onuchic, Herbert Levine
Summary: Multiple RNA polymerases (RNAPs) transcribing a gene can exhibit collective behavior, where the transcription elongation rate increases with the rate of transcription initiation. Recent studies suggest that even RNAPs separated by long distances can cooperate by modifying the DNA segment under transcription. This theoretical model incorporates the mechanical coupling between RNAP translocation and DNA torsional response, and stochastic simulations demonstrate DNA supercoiling-mediated long-range cooperation between co-transcribing RNAPs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Shubham Tripathi, Jun Hyoung Park, Shivanand Pudakalakatti, Pratip K. Bhattacharya, Benny Abraham Kaipparettu, Herbert Levine
Summary: Recent studies have shown that tumor cell metabolism is characterized by metabolic heterogeneity and plasticity. However, the field lacks a framework to analyze this heterogeneity and plasticity. Using a mechanistic model, researchers found that excess cytoplasmic ATP can drive a preference for aerobic glycolysis in fast-proliferating tumor cells, and the relative availability of glucose and glutamine can further drive metabolic heterogeneity. Additionally, the model can predict the metabolic and gene expression changes in cancer cells in response to drug treatment.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Cell Biology
Wen Jia, Mohit Kumar Jolly, Herbert Levine
Summary: The epithelial-mesenchymal transition (EMT) is a crucial cellular process for wound healing, cancer metastasis, and embryonic development. Recent studies have shown that hybrid epithelial/mesenchymal states, possessing both epithelial and mesenchymal traits, play a significant role in cancer metastasis and resistance to therapies. NRF2 has been identified as a stabilizing factor for these hybrid states. This research incorporates a phenomenological epigenetic feedback effect into a computational model for EMT signaling and demonstrates its stabilizing effect on the hybrid state if NRF2 influences SNAIL at an epigenetic level.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arin Nam, Atish Mohanty, Supriyo Bhattacharya, Sourabh Kotnala, Srisairam Achuthan, Kishore Hari, Saumya Srivastava, Linlin Guo, Anusha Nathan, Rishov Chatterjee, Maneesh Jain, Mohd W. Nasser, Surinder Kumar Batra, Govindan Rangarajan, Erminia Massarelli, Herbert Levine, Mohit Kumar Jolly, Prakash Kulkarni, Ravi Salgia
Summary: This study developed a mathematical approach based on game theory to model the response of non-small cell lung cancer cells to cisplatin treatment. The findings suggest that dynamic interactions and group behavior play a role in drug resistance, with tolerant cells displaying a 'persister-like' behavior and educating sensitive cells to evade chemotherapy. Furthermore, intermittent chemotherapy may be a better treatment strategy to reduce the emergence of tolerant cells in lung cancer.
Article
Biochemistry & Molecular Biology
Susmita Mandal, Tanishq Tejaswi, Rohini Janivara, Syamanthak Srikrishnan, Pradipti Thakur, Sarthak Sahoo, Priyanka Chakraborty, Sukhwinder Singh Sohal, Herbert Levine, Jason T. George, Mohit Kumar Jolly
Summary: The study compares three transcriptomic-based metrics for quantifying the extent of epithelial-mesenchymal plasticity (EMP) in cancer cells. The results show a high degree of concordance among these metrics in evaluating EMP, not only in cancer contexts but also in non-cancer contexts.
Article
Biochemistry & Molecular Biology
Srinath Muralidharan, Sarthak Sahoo, Aryamaan Saha, Sanjay Chandran, Sauma Suvra Majumdar, Susmita Mandal, Herbert Levine, Mohit Kumar Jolly
Summary: Research analysis reveals diverse associations between cancer cells' EMT status and metabolic pathways, showing that EMT is generally positively correlated with glycolysis but negatively correlated with oxidative phosphorylation and fatty acid metabolism. Additionally, higher levels of EMT and glycolysis predict a worse prognosis in many cancers.
Editorial Material
Multidisciplinary Sciences
Herbert Levine
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Samuel A. Vilchez Mercedes, Federico Bocci, Mona Ahmed, Ian Eder, Ninghao Zhu, Herbert Levine, Jose N. Onuchic, Mohit Kumar Jolly, Pak Kin Wong
Summary: In this study, the researchers used a combination of immunocytochemistry, single cell biosensors, and computational modeling to show that the transcription factor Nrf2 functions as a phenotypic stability factor for hybrid epithelial/mesenchymal cells during collective cancer migration. They also demonstrated that Nrf2 and EMT signaling are spatially coordinated near the leading edge, and that the Nrf2-EMT-Notch network enhances the expression of certain genes associated with the formation of leader cells and protruding tips.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Wen Jia, Atchuta Srinivas Duddu, Mohit Kumar Jolly, Herbert Levine
Summary: Biological cells can have different phenotypes determined by genetic networks, and the creation of landscapes is a popular way to represent these states. It is commonly believed that the landscape provides direct information about the state-to-state transition rates. However, this study shows that there is no direct correlation between the properties of the landscape and the corresponding transition rates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Physics, Multidisciplinary
David A. Kessler, Herbert Levine
Summary: Drug persistence is an important phenomenon in cancer treatment, and finding effective strategies to eliminate persister cells is crucial.
PHYSICAL REVIEW LETTERS
(2022)
Article
Multidisciplinary Sciences
Paras Jain, Sophia Corbo, Kulsoom Mohammad, Sarthak Sahoo, Santhalakshmi Ranganathan, Jason T. George, Herbert Levine, Joseph Taube, Michael Toneff, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) play crucial roles in embryonic development, wound healing, and cancer metastasis. While short-term EMT induction can lead to reversible phenotypic changes, long-term EMT induction is often associated with irreversibility. In this study, we demonstrate that the phenotypic changes observed in MCF10A cells during long-term EMT induction by TGF-beta can in fact have longer timescales of reversibility. We also propose a mathematical model that explains how the epigenetic memory gained during long-term EMT induction can slow down the recovery to the epithelial state after TGF-beta withdrawal.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Article
Physics, Fluids & Plasmas
David A. Kessler, Nadav M. Shnerb
Summary: This study aims to provide a comprehensive survey by examining a range of scenarios to understand the time distribution and fluctuations of population extinction. The researchers consider the impact of individual stochasticity on the extinction process and propose several generic criteria for classifying different experimental and empirical systems, thereby enhancing our understanding of the mechanisms governing extinction dynamics.
Article
Physics, Multidisciplinary
Pedram Esfahani, Herbert Levine, Mrinmoy Mukherjee, Bo Sun
Summary: Directed cell migration is crucial in various physiological and pathophysiological processes. This study investigates the migration of breast cancer cells in the presence of both contact guidance and a chemoattractant gradient. The results reveal that the microstructure of the extracellular matrix plays a complex role in cell chemotaxis. Coherent extracellular matrix fibers significantly enhance chemotaxis efficiency when contact guidance is parallel to the chemical gradient, while cells exploit ECM disorder to locate paths for chemotaxis when contact guidance is perpendicular to the chemical gradient.
PHYSICAL REVIEW RESEARCH
(2022)
Article
Oncology
Hiroko Masuda, Kenichi Harano, Sakiko Miura, Ying Wang, Yuko Hirota, Oi Harada, Mohit Kumar Jolly, Yuki Matsunaga, Bora Lim, Anita L. Wood, Napa Parinyanitikul, Hee Jin Lee, Gyungyub Gong, Jason T. George, Herbert Levine, Jangsoon Lee, Xiaoping Wang, Anthony Lucci, Arvind Rao, Brock L. Schweitzer, O. Rayne Lawrence, Robert S. Seitz, Stephan W. Morris, David R. Hout, Seigo Nakamura, Savitri Krishnamurthy, Naoto T. Ueno
Summary: The study found that TNBC molecular subtype and IM signature frequently change after NST, and the results suggest that EMT is promoted in the changed subtypes.
JCO PRECISION ONCOLOGY
(2022)