Review
Biochemistry & Molecular Biology
Longfu Xu, Matthew T. J. Halma, Gijs J. L. Wuite
Summary: Single-stranded DNA-binding proteins (SSBs) are essential for DNA metabolism and play crucial roles in maintaining genome integrity and coordinating with other proteins involved in DNA replication, recombination, and repair. Recent advances in single-molecule techniques and structural methods have greatly improved our understanding of the binding dynamics and interaction of SSBs with ssDNA and other protein partners. We highlight the central coordination role of SSBs in directly modulating the activities of other proteins and discuss the various modes of interaction between SSBs and their protein partners, providing a comprehensive view of the interaction network shaped by SSBs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Muwen Kong, Eric C. Greene
Summary: DNA double strand breaks are highly deleterious forms of DNA damage that, if left unrepaired, can lead to a high risk of cancer. Homologous recombination and nonhomologous end joining are the two major mechanisms responsible for repairing DSBs, and single-molecule studies have provided detailed insights into the repair processes at each step.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Parasitology
Christopher Notzel, Bjorn F. C. Kafsack
Summary: The Malaria Cell Atlas (MCA) aims to profile gene expression intensity and heterogeneity throughout the malaria parasite life cycle with single-cell resolution. Real et al. have now added the transmission stages of Plasmodium falciparum, the most virulent malaria parasite, to this user-friendly resource, completing the cycle.
TRENDS IN PARASITOLOGY
(2021)
Review
Behavioral Sciences
Naomi P. Friedman, Marie T. Banich, Matthew C. Keller
Summary: Twin/family studies and GWAS have their respective strengths and weaknesses, complementing and reinforcing each other rather than replacing one another.
TRENDS IN COGNITIVE SCIENCES
(2021)
Editorial Material
Psychology, Biological
Kelsey L. West, Kasey C. Soska, Whitney G. Cole, Danyang Han, Justine E. Hoch, Christina M. Hospodar, Brianna E. Kaplan
Summary: This commentary offers four guiding principles for conducting generalizable and enduring descriptive research.
BEHAVIORAL AND BRAIN SCIENCES
(2022)
Article
Chemistry, Analytical
Diana Soukarie, Philippe Rousseau, Maya Salhi, Alexia de Caro, Jean-Marc Escudier, Catherine Tardin, Vincent Ecochard, Laurence Salome
Summary: This study successfully developed an aptasensor based on high-throughput single-molecule techniques, which enables rapid, simple, and sensitive detection of single target molecules. The presence and concentration of the target molecules can be monitored in real time by combining videomicroscopy and image analysis.
ANALYTICAL CHEMISTRY
(2022)
Article
Quantum Science & Technology
Miriam Backens, Hector Miller-Bakewell, Giovanni de Felice, Leo Lobski, John van de Wetering
Summary: Translations between the quantum circuit model and the measurement-based one-way model are useful for verification and optimization of quantum computations. The newly developed algorithm allows for processing one-way computations containing measurements in all three planes and having gflow, resulting in efficient circuits without ancillae. This algorithm represents the most general known procedure for extracting circuits from ZX-diagrams and can be applied to circuit optimization.
Article
Multidisciplinary Sciences
Jason C. Bell, Christopher C. Dombrowski, Jody L. Plank, Ryan B. Jensen, Stephen C. Kowalczykowski
Summary: Mutations in the BRCA2 gene increase the risk of breast and ovarian cancers. This study shows that BRCA2 accelerates the formation of the RAD51 nucleoprotein filament, which plays a crucial role in DNA repair. BRCA2 also eliminates the kinetic barrier imposed by replication protein-A (RPA), allowing efficient and regulated recombination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Matthew A. Schaich, Bennett Van Houten
Summary: DNA is constantly threatened by various chemical and physical insults, requiring multiple repair pathways to maintain genome stability. Repair proteins' mechanisms of detecting damaged substrates in cellular chromatin remain unclear, but recent single-molecule techniques allow for visualization of damage search and detection processes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Plant Sciences
Patrick P. Edger, Massimo Iorizzo, Nahla Bassil, Juliana Benevenuto, Luis Felipe Ferrao, Lara Giongo, Kim Hummer, Lovely Mae F. Lawas, Courtney P. Leisner, Changying Li, Patricio R. Munoz, Hamid Ashrafi, Amaya Atucha, Ebrahiem M. Babiker, Elizabeth Canales, David Chagne, Lisa DeVetter, Mark Ehlenfeldt, Richard Espley, Karina Gallardo, Catrin S. Gunther, Michael Hardigan, Amanda M. Hulse-Kemp, MacKenzie Jacobs, Mary Ann Lila, Claire Luby, Dorrie Main, Molla F. Mengist, Gregory L. Owens, Penelope Perkins-Veazie, James Polashock, Marti Pottorff, Lisa J. Rowland, Charles A. Sims, Guo-qing Song, Jessica Spencer, Nicholi Vorsa, Alan E. Yocca, Juan Zalapa
Summary: The Vaccinium genus, which includes blueberries and cranberries, is culturally and economically important. This review article summarizes the research progress in taxonomy, genetics, genomics, and breeding of these berry crops and identifies future research areas and questions for crop improvement efforts.
HORTICULTURE RESEARCH
(2022)
Article
Chemistry, Analytical
Thomas Henkel, Guenter Mayer, Joerg Hampl, Jialan Cao, Linda Ehrhardt, Andreas Schober, Gregor Alexander Gross
Summary: Droplet-based microfluidic screening techniques can be connected to established microtiter plate-based screening and sample management workflows through interfacing tools. A bidirectional sampling interface for sample transfer from wells into droplets and vice versa droplets into wells is achieved using Digital Microfluidic Pipetting Tips (DMPT) and a robotic system.
Article
Chemistry, Physical
Terri E. Field-Theodore, Peter R. Taylor
Summary: The molecular species C3H4O presents a complex astrochemical puzzle, with only acrolein identified among over 60 possible structural isomers. Despite being a promising candidate, the detection of methylketene in astronomical observations has been unsuccessful. The study suggests new potential targets for observational astronomers in TMC-1 and provides accurate spectral data for interstellar searches.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Silvia Hormeno, Oliver J. Wilkinson, Clara Aicart-Ramos, Sahiti Kuppa, Edwin Antony, Mark S. Dillingham, Fernando Moreno-Herrero
Summary: Human DNA helicase B (HELB) plays important regulatory roles in DNA replication and recombination. It interacts with Replication Protein A (RPA) and RPA-single-stranded DNA (ssDNA) filaments to exhibit ATP hydrolysis translocation and helicase activities, and its ability to clear RPA from ssDNA allows other proteins to access these intermediates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Farhana Islam, Debayan Purkait, Padmaja Prasad Mishra
Summary: Single-molecule techniques have provided valuable insights into the molecular mechanisms of helicase activities, allowing researchers to study their real-time interactions, conformational intermediates, and motion at nanometer and millisecond resolutions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Review
Biochemistry & Molecular Biology
Rebeca Bocanegra, Ismael G. A. Plaza, Carlos R. Pulido, Borja Ibarra
Summary: The study reveals that the replisome machinery is stochastic, versatile, and highly dynamic, with transient protein-protein and protein-DNA interactions playing a key role in robust DNA replication.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Cell Biology
Christine M. Kondratick, M. Todd Washington, Maria Spies
Summary: DNA replication is complex and filled with obstacles that require decisions on whether to bypass, repair, restart damaged forks, or protect stalled forks. The involvement of multiple proteins in repair and restart mechanisms is crucial, but questions remain on how to ensure faithful genome duplication and prevent destabilization of the genome leading to cancer, cell death, and chemotherapeutic resistance. Various key players, including PCNA, DNA polymerases, molecular motors, and proteins involved in homologous recombination, play important roles in determining the mechanisms utilized to maintain genome integrity during DNA replication.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adam Hefel, Masayoshi Honda, Nicholas Cronin, Kailey Harrell, Pooja Patel, Maria Spies, Sarit Smolikove
Summary: RPA, a critical complex in replication and recombination, is composed of RPA-1, RPA-2, and RPA-3 subunits in most organisms. In Caenorhabditis elegans, RPA-2 is crucial for germline replication and repair of meiotic DSBs, while RPA-1 plays a key role in somatic replication. The formation of different RPA complexes is regulated in the nucleus, and RPA-4 inhibits RAD-51 filament formation and promotes apoptosis in damaged nuclei.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Joseph Tibbs, Mohamed Ghoneim, Colleen C. Caldwell, Troy Buzynski, Wayne Bowie, Elizabeth M. Boehm, M. Todd Washington, S. M. Ali Tabei, Maria Spies
Summary: Molecular machines within cells exhibit dynamic assembly, disassembly, and reorganization, with molecular interactions between components being observed and quantified through single-molecule level studies and fluorescence microscopy techniques. Analyzing sequences of molecular interactions can reveal the structure and dynamic organization of complexes, providing important insights into complex biological systems.
NUCLEIC ACIDS RESEARCH
(2021)
News Item
Biophysics
Maria Spies
BIOPHYSICAL JOURNAL
(2021)
Article
Biology
Barbara Stekas, Steve Yeo, Alice Troitskaia, Masayoshi Honda, Sei Sho, Maria Spies, Yann R. Chemla
Summary: Helicases use NTP hydrolysis to move along and unwind single-stranded nucleic acids in cells, often working in conjunction with other nucleic acid-associated proteins. By studying the interaction between XPD helicase and RPA2, it has been discovered that helicases can switch between different processive states, with transient RPA2 interactions stabilizing the more processive state. This finding sheds light on how accessory proteins regulate helicase activity.
Article
Biochemistry & Molecular Biology
John J. Skoko, Juxiang Cao, David Gaboriau, Myriam Attar, Alparslan Asan, Lisa Hong, Candice E. Paulsen, Hongqiang Ma, Yang Liu, Hanzhi Wu, Trey Harkness, Cristina M. Furdui, Yefim Manevich, Ciaran G. Morrison, Erika T. Brown, Daniel Normolle, Maria Spies, Michael Ashley Spies, Kate Carroll, Carola A. Neumann
Summary: This study identifies RAD51 Cys319 as a functionally significant site for the redox regulation of homologous recombination (HR) and cellular responses to ionizing radiation (IR). The loss of peroxiredoxin 1 (PRDX1) inhibits RAD51 focus formation and HR DNA repair, leading to increased DNA damage and sensitization of cells to irradiation.
Article
Genetics & Heredity
Divya S. Bhat, M. Ashley Spies, Maria Spies
Summary: BRCA-ness phenotype, a signature of many breast and ovarian cancers, offers opportunities for the development of novel chemotherapeutic interventions. PARP inhibitors have been approved for the treatment of patients with BRCA1/2 mutations, and other targets have been identified for selectively killing BRCA-deficient cancer cells.
Article
Biochemistry & Molecular Biology
Justin A. Ling, Melissa S. Gildenberg, Masayoshi Honda, Christine M. Kondratick, Maria Spies, M. Todd Washington
Summary: DNA damage bypass pathways promote replication of damaged DNA by converting stalled replication forks into four-way DNA junctions. Rad5 helicase is involved in this process and shows a preference for DNA substrates with short gaps in the leading strand. These substrates form intermediates that can be extended by replicative DNA polymerases during template switching.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Paras Gaur, Fletcher E. Bain, Masayoshi Honda, Sophie L. Granger, Maria Spies
Summary: As many as 700,000 unique sequences in the human genome can fold into G-quadruplexes (G4s), which play important roles in various cellular processes. A small protein called G4P has been synthesized and shown to bind G4 structures with better selectivity than previous methods. By studying its interaction with different G4s, the researchers found that increasing the number of recognition motifs in G4P enhances its affinity for certain G4s and its ability to interact with sequences containing multiple G4s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Divya S. Bhat, Eva Malacaria, Ludovica Di Biagi, Mortezaali Razzaghi, Masayoshi Honda, Kathryn F. Hobbs, Sarah R. Hengel, Pietro Pichierri, M. Ashley Spies, Maria Spies
Summary: The RAD52 protein is a promising target for anticancer drug discovery, especially in breast and ovarian cancers with defects in BRCA1 and BRCA2. The complex structure of RAD52 makes it difficult to develop drug-like leads using traditional medicinal chemistry approaches. However, by using pharmacophoric informatics and a database search, six chemical scaffolds that interact with RAD52 were identified, with two compounds selectively killing BRCA-mutant cells. Further optimization of one of the compounds resulted in more potent and selective inhibitors, providing a roadmap for the development of next-generation cancer therapeutics targeting RAD52.
Article
Biochemistry & Molecular Biology
Terence Gall-Duncan, Jennifer Luo, Carla-Marie Jurkovic, Laura A. Fischer, Kyota Fujita, Amit L. Deshmukh, Rachel J. Harding, Stephanie Tran, Mustafa Mehkary, Vanessa Li, David E. Leib, Ran Chen, Hikari Tanaka, Amanda G. Mason, Dominique Levesque, Mahreen Khan, Mortezaali Razzaghi, Tanya Prasolava, Stella Lanni, Nozomu Sato, Marie-Christine Caron, Gagan B. Panigrahi, Peixiang Wang, Rachel Lau, Arturo Lopez Castel, Jean-Yves Masson, Lynette Tippett, Clinton Turner, Maria Spies, Albert R. La Spad, Eric I. Campos, Maurice A. Curtis, Francois-Michel Boisvert, Richard L. M. Faull, Beverly L. Davidson, Masayuki Nakamori, Hitoshi Okazawa, Marc S. Wold, Christopher E. Pearson
Summary: Expansions of repeat DNA tracts can cause diseases and their progression in the brain. Two types of ssDNA-binding complexes, RPA and Alt-RPA, have different expressions and functions in the repair and expansion of slipped-DNAs, potentially impacting disease development.
Article
Biochemistry & Molecular Biology
Lisa Hong, Dennis C. Braden, Yaoning Zhao, John J. Skoko, Fei Chang, Steven R. Woodcock, Crystall Uvalle, Allison Casey, Katherine Wood, Sonia R. Salvatore, Alparslan Asan, Trey Harkness, Adeola Fagunloye, Mortezaali Razzaghi, Adam Straub, Maria Spies, Daniel D. Brown, Adrian Lee, Francisco Schopfer, Bruce A. Freeman, Carola A. Neumann
Summary: This study reveals a novel mechanism of action of nitroalkenes in treating triple-negative breast cancer (TNBC) by inhibiting homologous-recombination (HR)-mediated repair of DNA double-strand breaks (DSB). The researchers discovered two structurally different nitroalkenes (CP-8 and CP-23) that showed superior efficacy in killing TNBC cells and synergizing with PARP inhibitors.
Article
Oncology
Richa Sharma, Ninad Oak, Wenan Chen, Rose Gogal, Martin Kirschner, Fabian Beier, Michael J. Schnieders, Maria Spies, Kim E. Nichols, Marcin Wlodarski
Summary: The study found that germline variants affecting RPA1 are enriched in pediatric cancers, suggesting a potential role of these variants in oncogenesis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Khaliunaa Bayanbold, Mekhla Singhania, Melissa A. Fath, Charles C. Searby, Jeffrey M. Stolwijk, John B. Henrich, Casey F. Pulliam, Joshua D. Schoenfeld, Kranti A. Mapuskar, Sei Sho, Joseph M. Caster, Bryan G. Allen, Garry R. Buettner, Maria Spies, Prabhat C. Goswami, Michael S. Petronek, Douglas R. Spitz
Summary: Depletion of LIP can induce genomic instability, cell death, and enhance therapeutic responses to chemoradiation in lung cancer.
Article
Hematology
Richa Sharma, Sushree S. Sahoo, Masayoshi Honda, Sophie L. Granger, Charnise Goodings, Louis Sanchez, Axel Kunstner, Hauke Busch, Fabian Beier, Shondra M. Pruett-Miller, Marcus B. Valentine, Alfonso G. Fernandez, Ti-Cheng Chang, Vincent Geli, Dmitri Churikov, Sandrine Hirschi, Victor B. Pastor, Melanie Boerries, Melchior Lauten, Charikleia Kelaidi, Megan A. Cooper, Sarah Nicholas, Jill A. Rosenfeld, Sophia Polychronopoulou, Caroline Kannengiesser, Carole Saintome, Charlotte M. Niemeyer, Patrick Revy, Marc S. Wold, Maria Spies, Miriam Erlacher, Stephane Coulon, Marcin W. Wlodarski
Summary: This study identifies germline RPA1 variants in patients with TBD/STS and demonstrates the functional consequences of these variants. The findings suggest that these variants enhance DNA-binding function and impair hematopoietic differentiation. Somatic genetic rescue is also observed in some patients, leading to stabilized blood counts.
