Article
Biochemistry & Molecular Biology
Mai Wu, Tan Lin, Kunming Dong, Yong Gong, Xipeng Liu, Likui Zhang
Summary: This study characterizes a family IV uracil DNA glycosylase (Sis-UDGIV) from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A and investigates the roles of nine conserved residues in uracil excision and four conserved cysteine residues in maintaining protein conformation and stability. The results provide insights into the biochemical function and DNA-binding specificity of archaeal family IV UDGs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Microbiology
Peter B. Bohall, Stephen D. Bell
Summary: The loss of putative repair polymerases PolB2 and/or PolB3 in the crenarchaeon Sulfolobus islandicus leads to a modest growth advantage and insensitivity to hydrogen peroxide. However, cells lacking PolB3 show enhanced sensitivity to the DNA damaging agent 4-NQO, suggesting that these non-essential DNA polymerases may influence DNA repair pathway choice in hyperthermophilic aerobes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ryan J. J. Buckley, Anna Lou-Hing, Karl M. M. Hanson, Nadia R. R. Ahmed, Christopher D. O. Cooper, Edward L. L. Bolt
Summary: DNA glycosylases play a crucial role in maintaining genetic fidelity during DNA replication by eliminating chemically damaged DNA bases that could lead to mutations. In this study, researchers identified Lhr protein in Escherichia coli as a uracil-DNA glycosylase that is independent of its DNA helicase activity. The deletion of the lhr gene in E. coli sensitized cells to oxidative stress and increased cytosine deamination to uracil. This suggests that Lhr protein functions in surveillance and removal of potentially mutagenic base changes during replication stress.
MOLECULAR MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleem Syed, Frantisek Filandr, Jeffrey Patterson-Fortin, Albino Bacolla, Ramya Ravindranathan, Jia Zhou, Drew T. Mcdonald, Mohammed E. Albuhluli, Amy Verway-Cohen, Joseph A. Newman, Miaw-Sheue Tsai, Darin E. Jones, David C. Schriemer, Alan D. D'Andrea, John A. Tainer
Summary: Polymerase theta (Pol θ) is involved in DNA replication and repair, and its inhibition is deadly for BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB), an ATPase inhibitor of Pol θ, is being tested as an anti-cancer drug in clinical trials. This study reveals the molecular mechanism of NVB-mediated Pol θ inhibition, showing that NVB blocks DNA binding by binding to an allosteric site.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Likui Zhang, Donghao Jiang, Qi Gan, Haoqiang Shi, Li Miao, Yong Gong, Philippe Oger
Summary: Tba UDG247 is a novel bifunctional glycosylase that can excise uracil from DNA and further cleave the phosphodiester bond of the generated AP site. Kinetic analyses show that the enzyme has a faster rate for uracil excision than for AP cleavage, suggesting that cleaving AP site is a rate-limiting step for its bifunctionality.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Hiroka Miyabayashi, Hiroyuki D. Sakai, Norio Kurosawa
Summary: The subunits PBP1 and PBP2 greatly influence the activity of DNA polymerase PolB1, with PBP1 deletion leading to sensitivity to various types of DNA damage and increased mutation rate, while PBP2 is crucial for the replication process.
Article
Biochemistry & Molecular Biology
Komal Ghauri, Tjaard Pijning, Nayla Munawar, Hazrat Ali, Muhammad A. Ghauri, Munir A. Anwar, Russell Wallis
Summary: The crystal structure of an inulin-type fructan producing enzyme from the archaeon Halalkalicoccus jeotgali was resolved in this study, revealing unique features compared to previously reported FTFs. The high negative electrostatic surface potential of InuHj likely contributes to its halophilicity. The findings provide targets for future structure-function studies of FTF enzymes, especially those from archaea.
Article
Oncology
Gonzalo Rodriguez-Berriguete, Marco Ranzani, Remko Prevo, Rathi Puliyadi, Nicole Machado, Hannah R. Bolland, Val Millar, Daniel Ebner, Marie Boursier, Aurora Cerutti, Alessandro Cicconi, Alessandro Galbiati, Diego Grande, Vera Grinkevich, Jayesh B. Majithiya, Desiree Piscitello, Eeson Rajendra, Martin L. Stockley, Simon J. Boulton, Ester M. Hammond, Robert A. Heald, Graeme C. M. Smith, Helen M. R. Robinson, Geoff S. Higgins
Summary: This study evaluates the feasibility of targeting DNA polymerase theta (Pol theta) with novel small-molecule inhibitors to enhance the efficacy of radiotherapy. The results demonstrate that these inhibitors effectively radiosensitize tumor cells without affecting normal cells. Mechanistically, the inhibition of Pol theta impairs DNA damage repair, particularly in replicating cells. Additionally, these inhibitors can overcome hypoxia-induced radioresistance. In vivo experiments show that the combination of Pol theta inhibition with fractionated radiation is well-tolerated and significantly reduces tumor growth.
CLINICAL CANCER RESEARCH
(2023)
Article
Virology
Conor W. Templeton, Paula Traktman
Summary: Poxviruses remain of significant interest because of their continuing clinical relevance, their utility for the development of vaccines and oncolytic therapies, and their illustration of fundamental principles of viral replication and virus/cell interactions. These viruses are unique in that they replicate exclusively in the cytoplasm of infected mammalian cells, providing novel challenges for DNA viruses.
JOURNAL OF VIROLOGY
(2022)
Review
Oncology
Michal Gola, Przemyslaw Stefaniak, Janusz Godlewski, Barbara Alicja Jereczek-Fossa, Anna Starzynska
Summary: POLD1, a subunit of DNA polymerase delta complex, is crucial for DNA replication and repair. Its mutations have been found in various malignancies and its expression patterns have been associated with clinicopathological features. This review aims to summarize the current knowledge and future prospects of POLD1 in cancer research.
Article
Chemistry, Multidisciplinary
Abigail R. Orun, Ethan T. Shields, Sara Dmytriw, Ananya Vajapayajula, Caroline K. Slaughter, Christopher D. Snow
Summary: Researchers have designed isoreticular cocrystals as scaffolds for DNA-binding molecules. These cocrystals have tunable DNA-DNA junctions and can accommodate different guest molecules during crystallization. The design principles can be applied to existing cocrystals to develop programmable scaffolds for DNA-binding molecules.
Article
Biochemistry & Molecular Biology
Graeme Hewitt, Valerie Borel, Sandra Segura-Bayona, Tohru Takaki, Phil Ruis, Roberto Bellelli, Laura C. Lehmann, Lucia Sommerova, Aleksandra Vancevska, Antonia Tomas-Loba, Kang Zhu, Christopher Cooper, Kasper Fugger, Harshil Patel, Robert Goldstone, Deborah Schneider-Luftman, Ellie Herbert, Gordon Stamp, Rachel Brough, Stephen Pettitt, Christopher J. Lord, Stephen C. West, Ivan Ahel, Dragana Ahel, J. Ross Chapman, Sebastian Deindl, Simon J. Boulton
Summary: The loss of ALC1 increases sensitivity to PARP inhibitors, indicating the importance of nucleosome remodeling in DNA repair. ALC1 deficiency is synthetically lethal with homologous recombination deficiency, due to chromosome instability caused by unrepaired DNA gaps.
Article
Chemistry, Multidisciplinary
Constantin Giurgiu, Ziyuan Fang, Harry R. M. Aitken, Seohyun Chris Kim, Lydia Pazienza, Shriyaa Mittal, Jack W. Szostak
Summary: The research on the mechanism of RNA copying chemistry has revealed that deprotonation of the primer 3'-hydroxyl occurs before the rate-limiting step in RNA synthesis. Additionally, analogs with E-3 ribose conformation show the fastest formation of 3'-5' phosphodiester bonds, with the reaction rate strongly correlated with the electronegativity of the 2'-substituent.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Ying Yu, Junsong Guo, Zhengjun Cai, Yingchen Ju, Jun Xu, Qiong Gu, Huihao Zhou
Summary: This study utilized fragment screening and X-ray crystallography to identify new building blocks and binding mechanisms for the discovery of new GyrB inhibitors. Some chemical fragments were found to affect enzyme activity, providing new insights for the design of GyrB inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jeanine Rismondo, Robert M. Cleverley, Harriet V. Lane, Stephanie Grosshennig, Anne Steglich, Lars Moeller, Gopala Krishna Mannala, Torsten Hain, Richard J. Lewis, Sven Halbedel
MOLECULAR MICROBIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Andriy Kryshtafovych, John Moult, Arnaud Basle, Alex Burgin, Timothy K. Craig, Robert A. Edwards, Deborah Fass, Marcus D. Hartmann, Mateusz Korycinski, Richard J. Lewis, Donald Lorimer, Andrei N. Lupas, Janet Newman, Thomas S. Peat, Kurt H. Piepenbrink, Janani Prahlad, Mark J. van Raaij, Forest Rohwer, Anca M. Segall, Victor Seguritan, Eric J. Sundberg, Abhimanyu K. Singh, Mark A. Wilson, Torsten Schwede
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2016)
Article
Infectious Diseases
Robert M. Cleverley, Jeanine Rismondo, Michael P. Lockhart-Cairns, Paulien T. Van Bentum, Alexander J. F. Egan, Waldemar Vollmer, Sven Halbedel, Clair Baldock, Eefjan Breukink, Richard J. Lewis
MICROBIAL DRUG RESISTANCE
(2016)
Article
Microscopy
J. Robin Harris, Richard J. Lewis
Editorial Material
Biochemistry & Molecular Biology
Richard J. Lewis
MOLECULAR MICROBIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Arnaud Basle, Lorraine Hewitt, Alan Koh, Heather K. Lamb, Paul Thompson, J. Grant Burgess, Michael J. Hall, Alastair R. Hawkins, Heath Murray, Richard J. Lewis
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
William C. Wilson, Hue-Tran Hornig-Do, Francesco Bruni, Jeong Ho Chang, Alexis A. Jourdain, Jean-Claude Martinou, Maria Falkenberg, Henrik Spahr, Nils-Goeran Larsson, Richard J. Lewis, Lorraine Hewitt, Arnaud Basle, Harold E. Cross, Liang Tong, Robert R. Lebel, Andrew H. Crosby, Zofia M. A. Chrzanowska-Lightowlers, Robert N. Lightowlers
HUMAN MOLECULAR GENETICS
(2014)
Article
Microbiology
Christine Diethmaier, Joseph A. Newman, Akos T. Kovacs, Volkhard Kaever, Christina Herzberg, Cecilia Rodrigues, Mirjam Boonstra, Oscar P. Kuipers, Richard J. Lewis, Joerg Stuelke
JOURNAL OF BACTERIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Felix M. P. Mehne, Kathrin Schroeder-Tittmann, Robyn T. Eijlander, Christina Herzberg, Lorraine Hewitt, Volkhard Kaever, Richard J. Lewis, Oscar P. Kuipers, Kai Tittmann, Joerg Stuelke
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Immunology
Katarzyna M. Mickiewicz, Frances Gays, Richard J. Lewis, Colin G. Brooks
JOURNAL OF IMMUNOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Marret Mueller, Swantje Reiss, Rabea Schlueter, Ulrike Maeder, Anica Beyer, Wenke Reiss, Jon Marles-Wright, Richard J. Lewis, Henrike Pfoertner, Uwe Voelker, Katharina Riedel, Michael Hecker, Susanne Engelmann, Jan Pane-Farre
MOLECULAR MICROBIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Christopher N. Hoyland, Christine Aldridge, Robert M. Cleverley, Marie-Clemence Duchene, George Minasov, Olena Onopriyenko, Karzan Sidiq, Peter J. Stogios, Wayne F. Anderson, Richard A. Daniel, Alexei Savchenko, Waldemar Vollmer, Richard J. Lewis
Article
Biochemistry & Molecular Biology
Nicolas L. Jean, Catherine M. Bougault, Adam Lodge, Adeline Derouaux, Gilles Callens, Alexander J. F. Egan, Isabel Ayala, Richard J. Lewis, Waldemar Vollmer, Jean-Pierre Simorre
Article
Microbiology
Jan Kampf, Jan Gerwig, Kerstin Kruse, Robert Cleverley, Miriam Dormeyer, Alexander Gruenberger, Dietrich Kohlheyer, Fabian M. Commichau, Richard J. Lewis, Joerg Stuelke
Review
Biochemistry & Molecular Biology
Simon Booth, Richard J. Lewis
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)