Review
Biochemistry & Molecular Biology
Kazutoshi Kasho, Shogo Ozaki, Tsutomu Katayama
Summary: This review summarizes the mechanisms of timely binding and dissociation of nucleoid proteins IHF and Fis in chromosomal DNA replication initiation in Escherichia coli. The timely stabilization of IHF binding at oriC and the timely regulation of DnaA activity via DARS2 and datA are crucial for the timing control of replication initiation. IHF and Fis play specific roles in the regulation of replication initiation and proposed mechanisms for the regulation of timely IHF binding and dissociation at DARS2 and datA are discussed in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Microbiology
Inoka P. Menikpurage, Kristin Woo, Paola E. Mera
Summary: DnaA is the most conserved DNA replication initiator protein in bacteria, fulfilling crucial roles in chromosome replication initiation and gene expression regulation. Its dual functions, as both a replication initiator and transcription factor, provide a potential mechanism for coordinating diverse cellular events with the onset of chromosome replication. This strategy of utilizing replication initiator proteins as regulators of gene expression is also seen in archaea and eukaryotes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Nora Halgasova, Rachel Javorova, Lucia Bocanova, Daniela Krajcikova, Jacob A. Bauer, Gabriela Bukovska
Summary: The bacteriophage phiBP contains putative replisome organizer, helicase loader, and beta clamp that may play a role in DNA replication. Bioinformatics analysis found that the phiBP replisome organizer belongs to a newly identified family of initiator proteins. Recombinant proteins gpRO-HC and gpRO-HCK8A, with a lysine to alanine substitution at position 8, were prepared and studied. gpRO-HC showed low ATPase activity, regardless of DNA presence, while the mutant demonstrated significantly higher ATPase activity. gpRO-HC bound to both single- and double-stranded DNA substrates, forming higher oligomers composed of about 12 subunits. This study provides valuable information on phage initiator proteins involved in DNA replication in low GC Gram-positive bacteria.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ryusei Yoshida, Shogo Ozaki, Hironori Kawakami, Tsutomu Katayama
Summary: This study describes the unwinding mechanisms of the DUE in the replication origin oriC of Escherichia coli, which are promoted by DnaA, IHF, and the structural homolog HU. IHF and HU promote DUE unwinding by promoting the binding of R1/R5M-bound DnaAs to ssDUE. Notably, HU binds the R1-R5M interspace stimulated by ATP-DnaA and ssDUE, suggesting a model of DUE unwinding triggered by DnaA interactions and stabilized by HU binding.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sai Li, Michael R. Wasserman, Olga Yurieva, Lu Bai, Michael E. O'Donnell, Shixin Liu
Summary: This study found that the ORC can eject histones from a nucleosome in an ATP-dependent manner. It selectively evicts H2A-H2B dimers but leaves the (H3-H4)2 tetramer on DNA. It also discriminates canonical H2A from the H2A.Z variant, evicting the former while retaining the latter. These findings suggest that the ORC is a bona fide nucleosome remodeler that functions to create a local chromatin environment optimal for origin activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Godefroid Charbon, Belen Mendoza-Chamizo, Christopher Campion, Xiaobo Li, Peter Ruhdal Jensen, Jakob Frimodt-Moller, Anders Lobner-Olesen
Summary: Research has shown that in E. coli cells depleted of ATP, the initiator protein DnaA is degraded, leading to a block in chromosome replication initiation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Genetics & Heredity
Lilian Lanteri, Anthony Perrot, Diane Schausi-Tiffoche, Pei-Yun Jenny Wu
Summary: Eukaryotic DNA replication is regulated by conserved mechanisms, and changes in the position of replication origins along the chromosome can lead to alterations in the organization of DNA replication. However, large-scale genomic inversions surprisingly do not affect cell proliferation and meiotic progression, despite inducing restructuring of replication domains. The immediate chromosomal neighborhood of an origin is a crucial determinant of its activity.
Article
Biology
Farah Shahid, Youssef Saeed Alghamdi, Mutaib Mashraqi, Mohsin Khurshid, Usman Ali Ashfaq
Summary: Shigella sonnei is a major cause of diarrhea, and antibiotic therapy is crucial for reducing the prevalence and fatality rate of infections. This study utilized subtractive genomics to identify potential drug targets for S. sonnei, and suggested several phytochemicals as potential antibacterial drugs.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yanqi Hou, Pankaj Kumar, Monika Aggarwal, Farzad Sarkari, Karen M. Wolcott, Dhruba K. Chattoraj, Elliott Crooke, Rahul Saxena
Summary: This study found that the D118Q substitution in the linker domain of DnaA affects ATP binding and replication initiation. Overexpression of DnaA(D118Q) causes overinitiation of replication and prevents cell growth, which can be rescued by overexpression of SeqA. Additionally, small deletions in the linker domain allow cellular growth without requiring normal levels of anionic membrane lipids, similar to the properties of DnaA mutated in its ATPase domain.
Review
Microbiology
Julia E. Grimwade, Alan C. Leonard
Summary: Genome duplication is a critical event in the reproduction cycle of every cell, regulated by multiple mechanisms controlling when chromosome replication begins. In Escherichia coli, assembly of orisomes involves transcriptional modulators that interact with the oriC to regulate DnaA binding and ensure that chromosome replication occurs once per cell cycle. These regulators function by blocking sites, bending DNA, and modulating protein levels according to growth rate, ultimately contributing to the strict control of bacterial chromosome replication.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Katja Becker, Andreas Meyer, Tania Michelle Roberts, Sven Panke
Summary: In this study, T7 RNA polymerase is found to be necessary for the replication of T7 on plasmids, while T7 replication proteins are dispensable. The system is shown to be portable among different plasmid architectures and ribonuclease H-inactivated E. coli strains. Additionally, the copy number of T7 ori plasmids can be adjusted based on the induction level of RNAP.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lucia Falbo, Vincenzo Costanzo
Summary: Research has shown that in early embryonic development of certain metazoans, there is a transition in the number of replication origins to ensure accurate DNA replication. This novel form of epigenetic memory may impact various areas of vertebrate biology.
Article
Multidisciplinary Sciences
Mareike Berger, Pieter Rein ten Wolde
Summary: The study investigates the replication initiation cycles of Escherichia coli at different growth rates and reveals that both the titration mechanism and the activation switch play crucial roles in driving stable replication cycles.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ganesh K. Maurya, Reema Chaudhary, Neha Pandey, Hari S. Misra
Summary: Deinococcus radiodurans harbors a multipartite ploid genome system with two chromosomes and two plasmids, but how these elements are maintained and inherited is not well understood. The pleiotropic protein PprA has been shown to regulate the ploidy of the chromosomes and inhibit the activity of the initiator protein drDnaA, which suggests that PprA plays a role as a checkpoint regulator for DNA replication initiation in D. radiodurans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Hsiang-Chen Chou, Kuhulika Bhalla, Osama El Demerdesh, Olaf Klingbeil, Kaarina Hanington, Sergey Aganezov, Peter Andrews, Habeeb Alsudani, Kenneth Chang, Christopher R. Vakoc, Michael C. Schatz, W. Richard McCombie, Bruce Stillman
Summary: Each subunit of ORC and CDC6 is essential in human cells, with their deficiency leading to difficulties in DNA replication initiation and cell division cycle progression, as well as abnormal nuclear and cell morphology.
Review
Biochemistry & Molecular Biology
Prashasti Kumar, Pratul K. Agarwal, Matthew J. Cuneo
Summary: Hydrogen plays a central role in biology, but due to difficulties in precisely determining its location, research on short hydrogen bonds has been controversial. Studies suggest that unique hydrogen bonds play a special role in biology.
Article
Chemistry, Multidisciplinary
Charl J. Jafta, Xiao-Guang Sun, Hailong Lyu, Hao Chen, Bishnu P. Thapaliya, William T. Heller, Matthew J. Cuneo, Richard T. Mayes, Mariappan Parans Paranthaman, Sheng Dai, Craig A. Bridges
Summary: The formation of the solid electrolyte interphase (SEI) in an ionic liquid electrolyte of 0.5 M lithium bis(fluorosulfonyl)imide (LiFSI) in 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide at high cell voltages (1.7-1.9 V) was investigated in ordered mesoporous carbon (OMC) based Li metal cells using an operando small-angle neutron scattering (SANS) technique coupled with electrochemical impedance spectroscopy and ex situ X-ray photoelectron spectroscopy (XPS). It was demonstrated that discharging the OMC Li metal cells to approximately 2 V and holding the cell voltage constant induces a rapid current increase with time, confirming extensive reduction and SEI formation. XPS analysis revealed that LiF is formed at open cell voltage (OCV), attributed to the carbenes generated at the lithium negative electrode reacting with EMIm cation diffusing to and initiating the reaction with FSI- anions at the carbon positive electrode. It was confirmed that the chemical reaction at OCV and electrochemical reduction at high cell voltage of the FSI- anion plays a protective role against EMIm cation co-intercalation into the carbon positive electrode during the initial discharge. Operando SANS studies also suggest that slight differences occur in the surface composition and reaction mechanism as a function of cell voltage.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Daniel T. Murray, Kevin L. Weiss, Christopher B. Stanley, Gergely Nagy, M. Elizabeth Stroupe
Summary: The study presents the solution structures of Sulfite reductase (SiR) heterodimers, showing how the subunits bind and how both subunit binding and oxidation state impact SiRF's conformation. SiRHP binding induces a change in SiRFP's position, while reduction of SiRFP leads to a more open structure for electron transfer between the subunits. These results provide insights into the mechanisms of electron transfer within SiR.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Erik W. Martin, F. Emil Thomasen, Nicole M. Milkovic, Matthew J. Cuneo, Christy R. Grace, Amanda Nourse, Kresten Lindorff-Larsen, Tanja Mittag
Summary: The study demonstrates that the interaction between folded and disordered domains can modulate the phase separation behavior of the RNA-binding protein hnRNPA1, even in the absence of RNA. The presence of folded domains can alter the salt dependence of phase separation, and the mechanism of interaction with the LCD provides an explanation for the observed salt-dependent phase separation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Andrew E. Blanchard, Christopher Stanley, Debsindhu Bhowmik
Summary: This study introduces a new approach to training GANs using concepts from Genetic Algorithms to promote incremental exploration and limit the impacts of mode collapse, outperforming traditional methods by replacing training data samples with valid samples from the generator, leading to a significant increase in potential applications for GANs in drug discovery.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Polymer Science
Xuechen Yin, David R. O. Hewitt, Bingqian Zheng, Suan P. Quah, Christopher B. Stanley, Robert B. Grubbs, Surita R. Bhatia
Summary: This study presents the nanoscale assembly of PLA-PEOPLA triblock copolymers in water, with a focus on the effect of stereochemistry on micellar properties. Different L/D ratios of PLA blocks were found to impact aggregation numbers and interactions between PLA chains, demonstrating the potential for tuning micellar properties for specific applications.
Editorial Material
Biochemistry & Molecular Biology
Matthew J. Cuneo, Tanja Mittag
Summary: Chromosomal translocations can generate fusion proteins that assemble cytoplasmic protein granules, leading to RAS signaling activation independent of lipid membranes.
Article
Biophysics
Daniel T. Murray, Nidhi Walia, Kevin L. Weiss, Christopher B. Stanley, Peter S. Randolph, Gergely Nagy, M. Elizabeth Stroupe
Summary: This study aimed to investigate the higher-order assembly structure of SiR by using deuterium labeling, in vitro reconstitution, analytical ultracentrifugation, small-angle neutron scattering, and neutron contrast variation. The results revealed that SiR is a flexible dodecamer with mismatched subunit stoichiometry. Furthermore, the study showed that SiRFP undergoes compaction upon assembly, while SiRHP adopts multiple positions in the complex. The obtained structure map supported a cis/trans mechanism for electron transfer between domains of reductase subunits and between reductase and oxidase subunits.
BIOPHYSICAL JOURNAL
(2022)
Article
Oncology
Hong-Jun Yoon, Christopher Stanley, J. Blair Christian, Hilda B. Klasky, Andrew E. Blanchard, Eric B. Durbin, Xiao-Cheng Wu, Antoinette Stroup, Jennifer Doherty, Stephen M. Schwartz, Charles Wiggins, Mark Damesyn, Linda Coyle, Georgia D. Tourassi
Summary: With the advancement of AI and machine learning in biomedical informatics, the concern for data security and privacy has become crucial. This study aims to quantify the privacy vulnerability of deep learning models for information extraction from medical textural contents, and propose ways to secure patients' information. Results show that the proposed vocabulary selection methods reduce privacy vulnerability while maintaining clinical task performance.
Article
Computer Science, Software Engineering
William T. Heller, John Hetrick, Jean Bilheux, Jose M. Borreguero Calvo, Wei-Ren Chen, Lisa DeBeer-Schmitt, Changwoo Do, Mathieu Doucet, Michael R. Fitzsimmons, William F. Godoy, Garrett E. Granroth, Steven Hahn, Lilin He, Fahima Islam, Jiao Lin, Kenneth C. Littrell, Marshall McDonnell, Jesse McGaha, Peter F. Peterson, Sai Venkatesh Pingali, Shuo Qian, Andrei T. Savici, Yingrui Shang, Christopher B. Stanley, Volker S. Urban, Ross E. Whitfield, Chen Zhang, Wenduo Zhou, Jay Jay Billings, Matthew J. Cuneo, Ricardo M. Ferraz Leal, Tianhao Wang, Bin Wu
Summary: This article describes the drtsans software package developed at Oak Ridge National Laboratory for data reduction in small-angle neutron scattering experiments. The software has positively impacted the scientific programs on the EQ-SANS, GP-SANS, and Bio-SANS instruments.
Proceedings Paper
Computer Science, Theory & Methods
Srikanth Yoginath, Mathieu Doucet, Debsindhu Bhowmik, David Heise, Folami Alamudun, Hong-Jun Yoon, Christopher Stanley
Summary: In a secure collaborative environment, tera-bytes of data generated from powerful scientific instruments are used to train secure machine learning models, which are then shared as cloud-based services with internal or external collaborators. This secure platform is necessary for seamless scientific knowledge sharing without compromising intellectual property and privacy. It enables new computing opportunities with sensitive data and accelerates scientific discovery.
DRIVING SCIENTIFIC AND ENGINEERING DISCOVERIES THROUGH THE INTEGRATION OF EXPERIMENT, BIG DATA, AND MODELING AND SIMULATION
(2022)
Proceedings Paper
Computer Science, Artificial Intelligence
Serena H. Chen, M. Todd Young, John Gounley, Christopher Stanley, Debsindhu Bhowmik
Summary: The study uses artificial intelligence and molecular dynamics simulation to analyze the structure of the S protein of the novel coronavirus. The research reveals the flexibility of the S protein structure and identifies key regions that may be potential targets for therapeutic development. Additionally, similarities in immunodominant sites between different coronaviruses are highlighted, offering insight for effective treatment strategies for COVID-19.
2021 IEEE INTERNATIONAL CONFERENCE ON BIG DATA (BIG DATA)
(2021)
Proceedings Paper
Engineering, Biomedical
Abhishek K. Dubey, Michael T. Young, Christopher Stanley, Dalton Lunga, Jacob Hinkle
Summary: Deep learning models are being deployed in medical centers to assist radiologists in diagnosing lung conditions from chest radiographs. However, the ability of pre-trained models to generalize in clinical settings is limited due to changes in data distributions and equipment heterogeneity. A domain-shift detection and removal method is introduced to overcome this issue, showing effectiveness in abnormality detection in chest radiographs in a clinical setting.
BIOIMAGING: PROCEEDINGS OF THE 14TH INTERNATIONAL JOINT CONFERENCE ON BIOMEDICAL ENGINEERING SYSTEMS AND TECHNOLOGIES - VOL. 2: BIOIMAGING
(2021)