Review
Biochemistry & Molecular Biology
Yilun Sun, John L. Nitiss, Yves Pommier
Summary: Topoisomerases play crucial roles in DNA metabolism by manipulating DNA structures and are regulated by post-translational modifications. Damage repair of topoisomerase malfunction is also regulated by various conditions and modifications.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Maja Kokot, Irena Zdovc, Marko Anderluh, Martina Hrast, Nikola Minovski
Summary: Novel bacterial topoisomerase inhibitors (NBTIs) with reduced hERG inhibition and potent antibacterial activity were designed and synthesized in this study. Structural features, such as the polarity of linker moieties, were found to influence the hERG inhibitory activity of NBTIs.
BIOORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Josephine Geertsen Keller, Karol Mizielinski, Kamilla Vandso Petersen, Magnus Stougaard, Birgitta R. Knudsen, Cinzia Tesauro
Summary: Isothermal amplification-based techniques like rolling circle amplification have been successfully used for detecting nucleic acids, protein quantities, and other molecules. These methods provide substantial alternatives to PCR or ELISA in clinical and research settings. Additionally, measuring enzyme activity offers valuable biomarkers for cancer diagnosis and the potential treatment of pathogen-borne diseases. Rolling circle enhanced enzyme activity detection (REEAD) assay enables quantitative measurement of topoisomerase 1 (TOP1) activity in a simple, fast, and gel-free manner through a specially designed DNA substrate, making it highly sensitive and directly quantitative.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Review
Chemistry, Inorganic & Nuclear
Manisha Gaikwad, V. Badireenath Konkimalla, Sunita Salunke-Gawali
Summary: The topoisomerase family plays a crucial role in maintaining DNA topology during cellular processes. Inhibition of these enzymes can be achieved through the use of metal complexes, which provide a three-dimensional framework for increased selectivity. This review focuses on the metal complexes that exhibit topoisomerase inhibition activity and their IC50 values.
INORGANICA CHIMICA ACTA
(2022)
Article
Multidisciplinary Sciences
Shar-yin N. Huang, Stephanie A. Michaels, Brianna B. Mitchell, Nadim Majdalani, Arnaud Vanden Broeck, Andres Canela, Yuk-Ching Tse-Dinh, Valerie Lamour, Yves Pommier
Summary: The study demonstrates that exonuclease VII (ExoVII) is important for repairing damage to prokaryotic type IIA topoisomerases, and bacteria deficient in ExoVII exhibit hypersensitivity to quinolone antibiotics. Additionally, an ExoVII inhibitor has been identified that synergizes with quinolones, including in quinolone-resistant bacterial strains.
Article
Cell Biology
Julian Kanne, Michelle Hussong, Joerg Isensee, Alvaro Munoz-Lopez, Jan Wolffgramm, Felix Hess, Christina Grimm, Sergey Bessonov, Lydia Meder, Jie Wang, H. Christian Reinhardt, Margarete Odenthal, Tim Hucho, Reinhard Buettner, Daniel Summerer, Michal R. Schweiger
Summary: Non-coding RNA from pericentromeric satellite repeats, specifically SatIII, plays a crucial role in lung cancer drug resistance, possibly through mechanisms related to genome stability, cancer therapy, and endogenous stress response processes.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Analytical
Alexandra Bogozalec Kosir, Dane Luznik, Viktorija Tomic, Mojca Milavec
Summary: The detection and quantification of DNA biomarkers heavily depend on the yield and quality of DNA extracted from various matrices. In this study, five extraction methods were compared for their efficiency in extracting DNA from sputum samples containing three different Gram-negative bacteria using digital PCR. The evaluation revealed that although the GXT NA extraction kit and CTAB method had the highest DNA yield, they did not meet the strict criteria for repeatability, intermediate precision, and measurement uncertainty. Despite this, considering the limited availability of clinical samples, the GXT NA extraction kit was determined to be the preferred method. The study also highlighted the usefulness of dPCR in assessing extraction method repeatability and the impact of DNA extraction methods on measurement uncertainty.
Article
Chemistry, Medicinal
Preshendren Govender, Rudolf Muller, Kawaljit Singh, Virsinha Reddy, Charles J. Eyermann, Stephen Fienberg, Sandeep R. Ghorpade, Lizbe Koekemoer, Alissa Myrick, Dirk Schnappinger, Curtis Engelhart, Jaclynn Meshanni, Jo Ann W. Byl, Neil Osheroff, Vinayak Singh, Kelly Chibale, Gregory S. Basarab
Summary: The study found that new spiropyrimidinetriones (SPTs) compounds have high inhibitory potency against drug-resistant Mycobacterium tuberculosis and may have potential therapeutic value for drug-resistant tuberculosis. These compounds exert antimicrobial effects by stabilizing double-cleaved DNA of the DNA gyrase and show high selectivity against drug-resistant tuberculosis bacteria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Diane T. Takahashi, Daniele Gadelle, Keli Agama, Evgeny Kiselev, Hongliang Zhang, Emilie Yab, Stephanie Petrella, Patrick Forterre, Yves Pommier, Claudine Mayer
Summary: In this study, the structure of archaeal CsTOP1 in the absence of DNA was solved, revealing an open conformation resulting from a rotation between the CAP and CAT modules. The flexibility of the hinge, a five-residue loop connecting these modules, allows the opening/closing of the enzyme and the entry of DNA. A conserved tyrosine near the hinge was identified as mediating the transition from the open to closed conformation upon DNA binding.
NATURE COMMUNICATIONS
(2022)
Review
Geriatrics & Gerontology
Morgan Crewe, Ram Madabhushi
Summary: The nervous system is susceptible to genomic instability and mutations in DNA damage response factors can lead to neurological disorders. The main sources and mechanisms of DNA damage relevant to neuronal dysfunction are not well understood. Topoisomerase-mediated DNA damage may be a significant underlying source of neuronal dysfunction.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Federica Dell'Annunziata, Carmela Dell'Aversana, Nunzianna Doti, Giuliana Donadio, Fabrizio Dal Piaz, Viviana Izzo, Anna De Filippis, Marilena Galdiero, Lucia Altucci, Giovanni Boccia, Massimiliano Galdiero, Veronica Folliero, Gianluigi Franci
Summary: Gram-negative bacteria release Outer Membrane Vesicles (OMVs) as vectors for horizontal gene transfer, particularly transferring plasmids containing resistance genes from Klebsiella pneumoniae (K. pneumoniae). The transfer is influenced by the plasmid copy number and the identity of the plasmid. K. pneumoniae-OMVs can transfer plasmids between species regardless of their phylogenetic characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Kalinga Pavan T. Silva, Ganesh Sundar, Anupama Khare
Summary: Antibiotics with multiple cellular targets were expected to reduce the occurrence of drug resistance. However, the study of adaptive trajectories and resistance mechanisms against these antibiotics is still insufficient. In this study, we investigated these issues using methicillin resistant Staphylococcus aureus (MRSA) exposed to delafloxacin (DLX), a novel multi-targeting antibiotic. We found that mutations and genomic amplifications in the gene encoding the efflux pump SdrM led to high DLX resistance, bypassing the need for mutations in the target enzymes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Julia A. M. Bakx, Andreas S. Biebricher, Graeme A. King, Panagiotis Christodoulis, Kata Sarlos, Anna H. Bizard, Ian D. Hickson, Gijs J. L. Wuite, Erwin J. G. Peterman
Summary: Topoisomerase IIIa is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. In this study, the authors used optical tweezers and fluorescence microscopy to investigate the catalytic steps of TRR. They found that TRR forms an open gate in single-stranded DNA and can bind a second single-stranded or double-stranded DNA molecule, leading to catenation. Interestingly, double-stranded DNA binding increases the gate size and the helicase BLM affects the flexibility of the gate. These findings suggest that TRR-mediated transfer of double-stranded DNA may be more important than previously believed.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ivina P. de Souza, Ariane C. C. de Melo, Bernardo L. Rodrigues, Adailton Bortoluzzi, Simon Poole, Zara Molphy, Vickie McKee, Andrew Kellett, Rodrigo B. Fazzi, Ana M. da Costa Ferreira, Elene C. Pereira-Maia
Summary: Five ternary copper(II) complexes were synthesized and characterized. Two complexes showed strong anti-cancer activity and DNA cleavage ability.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Review
Multidisciplinary Sciences
Liis Uuskula-Reimand, Michael D. Wilson
Summary: This review provides an updated overview of the roles of TOP2A and TOP2B in chromatin topology and transcription regulation, and discusses the recent discoveries linking TOP2 activities with cancer pathogenesis.
Article
Biochemistry & Molecular Biology
Ivan Laponogov, Xiao-Su Pan, Dennis A. Veselkov, Ryan T. Cirz, Allan Wagman, Heinz E. Moser, L. Mark Fisher, Mark R. Sanderson
Article
Multidisciplinary Sciences
Ivan Laponogov, Xiao-Su Pan, Dennis A. Veselkov, Galyna B. Skamrova, Trishant R. Umrekar, L. Mark Fisher, Mark R. Sanderson
NATURE COMMUNICATIONS
(2018)
Article
Microbiology
Xiao-Su Pan, Katherine A. Gould, L. Mark Fisher
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2009)
Article
Infectious Diseases
Emmanuelle Cambau, Stephanie Matrat, Xiao-Su Pan, Romain Roth Dit Bettoni, Celine Corbel, Alexandra Aubry, Christine Lascols, Jean-Yves Driot, L. Mark Fisher
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2009)
Article
Biochemistry & Molecular Biology
Ivan Laponogov, Maninder K. Sohi, Dennis A. Veselkov, Xiao-Su Pan, Ritica Sawhney, Andrew W. Thompson, Katherine E. McAuley, L. Mark Fisher, Mark R. Sanderson
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2009)
Article
Biochemistry & Molecular Biology
Xiao Su Pan, Miriam Dias, Manlio Palumbo, L. Mark Fisher
NUCLEIC ACIDS RESEARCH
(2008)
Article
Biochemistry & Molecular Biology
Elisa Arnoldi, Xiao-Su Pan, L. Mark Fisher
NUCLEIC ACIDS RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
Ivan Laponogov, Dennis A. Veselkov, Isabelle M. -T. Crevel, Xiao-Su Pan, L. Mark Fisher, Mark R. Sanderson
NUCLEIC ACIDS RESEARCH
(2013)
Article
Multidisciplinary Sciences
Maninder K. Sohi, Dennis A. Veselkov, Ivan Laponogov, Xiao-Su Pan, L. Mark Fisher, Mark R. Sanderson
Article
Multidisciplinary Sciences
Ivan Laponogov, Xiao-Su Pan, Dennis A. Veselkov, Katherine E. McAuley, L. Mark Fisher, Mark R. Sanderson
Article
Chemistry, Medicinal
Colin K. Skepper, Duncan Armstrong, Carl J. Balibar, Daniel Bauer, Cornelia Bellamacina, Bret M. Benton, Dirksen Bussiere, Gianfranco De Pascale, Javier De Vicente, Charles R. Dean, Bhavesh Dhumale, L. Mark Fisher, John Fuller, Mangesh Fulsunder, Lauren M. Holder, Cheng Hu, Bhavin Kantariya, Guillaume Lapointe, Jennifer A. Leeds, Xiaolin Li, Peichao Lu, Anatoli Lvov, Sylvia Ma, Shravanthi Madhavan, Swapnil Malekar, David McKenney, Wosenu Mergo, Louis Metzger, Heinz E. Moser, Daniel Mutnick, Jonas Noeske, Colin Osborne, Ashish Patel, Darshit Patel, Tushar Patel, Krunal Prajapati, Katherine R. Prosen, Folkert Reck, Daryl L. Richie, Alice Rico, Mark R. Sanderson, Shailesh Satasia, William S. Sawyer, Jogitha Selvarajah, Nirav Shah, Kartik Shanghavi, Wei Shu, Katherine Thompson, Martin Traebert, Anand Vala, Lakhan Vala, Dennis A. Veselkov, Jason Vo, Michael Wang, Marcella Widya, Sarah L. Williams, Yongjin Xu, Qin Yue, Richard Zang, Bo Zhou, Alexey Rivkin
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Guillaume Lapointe, Colin K. Skepper, Lauren M. Holder, Duncan Armstrong, Cornelia Bellamacina, Johanne Blais, Dirksen Bussiere, Jianwei Bian, Cody Cepura, Helen Chan, Charles R. Dean, Gianfranco De Pascale, Bhavesh Dhumale, L. Mark Fisher, Mangesh Fulsunder, Bhavin Kantariya, Julie Kim, Sean King, Lauren Kossy, Upendra Kulkarni, Jay Lakshman, Jennifer A. Leeds, Xiaolan Ling, Anatoli Lvov, Sylvia Ma, Swapnil Malekar, David McKenney, Wosenu Mergo, Louis Metzger, Keshav Mhaske, Heinz E. Moser, Mina Mostafavi, Sunil Namballa, Jonas Noeske, Colin Osborne, Ashish Patel, Darshit Patel, Tushar Patel, Philippe Piechon, Valery Polyakov, Krunal Prajapati, Katherine R. Prosen, Folkert Reck, Daryl L. Richie, Mark R. Sanderson, Shailesh Satasia, Bhautik Savani, Jogitha Selvarajah, Vijay Sethuraman, Wei Shu, Kyuto Tashiro, Katherine Thompson, Krishniah Vaarla, Lakhan Vala, Dennis A. Veselkov, Jason Vo, Bhavesh Vora, Trixie Wagner, Laura Wedel, Sarah L. Williams, Satya Yendluri, Qin Yue, Aregahegn Yifru, Yong Zhang, Alexey Rivkin
Summary: This study describes the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV by binding to and stabilizing DNA cleavage complexes. Compound 25, identified through optimization of this series, shows potent activity against Gram-positive bacteria, favorable in vitro safety profile, and excellent in vivo pharmacokinetic properties. The X-ray crystal structure of the ternary complex formed by topoisomerase IV, compound 25, and cleaved DNA suggests a structural basis for the reduced impact of QRDR mutations on the antibacterial activity of 25 compared to fluoroquinolones.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sara N. Richter, Giulia Giaretta, Valentina Comuzzi, Elisabetta Leo, Lesley A. Mitchenall, L. Mark Fisher, Anthony Maxwell, Manlio Palumbo
NUCLEIC ACIDS RESEARCH
(2007)
Article
Multidisciplinary Sciences
Ivan Laponogov, Dennis A. Veselkov, Maninder K. Sohi, Xiao-Su Pan, Aniruddha Achari, Cheng Yang, Joseph D. Ferrara, L. Mark Fisher, Mark R. Sanderson
