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Outcomes of Adolescents and Young Adults Compared with Children with Acute Leukemia after Single-Unit Unrelated Cord Blood Transplantation Using Myeloablative Conditioning without Antithymocyte Globulin.

Acta Haematol 2021 Apr 13:1-11. Epub 2021 Apr 13.

Department of Hematology, Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain.

Methods: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG).

Results: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. Read More

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Single cell spectroscopy of red blood cells in intravenous crystalloid fluids.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 19;257:119726. Epub 2021 Mar 19.

Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India. Electronic address:

Crystalloid fluids, a subset of intravenous (IV) fluid solutions are commonly used in clinical settings. The influence of these fluids on the functions of blood components are least explored. Raman spectroscopy combined with optical trapping has been widely used to evaluate the impact of external stress agents on red blood cells. Read More

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Ultrathin chalcogenide nanosheets for photoacoustic imaging-guided synergistic photothermal/gas therapy.

Biomaterials 2021 Apr 7;273:120807. Epub 2021 Apr 7.

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China. Electronic address:

Previous preclinical and clinical studies have shown that using only a single therapy makes it difficult to completely eradicate tumors and restrain cancer metastasis. To overcome this challenge, multi-modal synergistic treatments have attracted considerable attention. Herein, an ultrathin Cu-loaded CoCuFe-selenide (CCFS) was prepared by a facile topotactic transformation from CoCuFe layered double hydroxide (LDH) nanosheets (NSs), followed by surface modification with polyvinyl pyrrolidone (PVP) and l-arginine (L-Arg). Read More

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Dysiscalarones A-E, scalarane sesterterpenoids with nitric oxide production inhibitory activity from marine sponge Dysidea granulosa.

Bioorg Chem 2021 Mar 5;111:104791. Epub 2021 Mar 5.

Research Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address:

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264. Read More

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Characterization of mandarin fish (Siniperca chuatsi) IL-6 and IL-6 signal transducer and the association between their SNPs and resistance to ISKNV disease.

Fish Shellfish Immunol 2021 Apr 10. Epub 2021 Apr 10.

Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Provinces, Guangzhou, 510380, China.

In fish, interleukin-6 (IL-6) is a very important immune-regulatory cytokine that plays a polyfunctional role in inflammation, metabolism, regeneration, and neural processes. IL-6 signal transducer (IL-6ST) is a specific receptor for IL-6 and expressed mainly in immune cells and hepatocytes. In this study, the complete cDNA and genomic DNA sequences of mandarin fish (Siniperca chuatsi) IL-6 and IL-6ST genes were identified and analyzed. Read More

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Gut-specific arylphorin mediates midgut regenerative response against cry-induced damage in Achaea janata.

Comp Biochem Physiol B Biochem Mol Biol 2021 Apr 10:110600. Epub 2021 Apr 10.

Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Ghudda, Bathinda 151401, India.

Development of insect resistance to biopesticides is a current and pertinent global issue. Earlier, it was established that lepidopteran larvae can recover from Bt intoxication via a midgut regenerative response and subsequently generate resistance. Molecular aspects of restoration of the midgut integrity following toxin exposure are emerging recently. Read More

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Optical and Genetic Tools for in vivo Single Cell Tracking.

J Neurosci Methods 2021 Apr 10:109192. Epub 2021 Apr 10.

Instituto Cajal, CSIC, Ave. Doctor Arce, 37, Madrid, 28002 Spain.

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Defining Optimal Enzyme and Matrix Combination for Replating of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes at Different Levels of Maturity.

Exp Cell Res 2021 Apr 10:112599. Epub 2021 Apr 10.

Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey; Department of Medical Biology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey; Medical Biology and Genetics Graduate Program, Health Sciences Institute, Istanbul Medipol University, Istanbul, Turkey. Electronic address:

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) create an unlimited cell source for basic and translational research. Depending on the maturity of cardiac cultures and the intended downstream application, obtaining hiPSC-CMs as a single-cell, monolayer or three-dimensional clusters can be challenging. Here, we defined strategies to replate hiPSC-CMs on early days (D15-30) or later more mature (D60-150) differentiation cultures. Read More

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Independent evolution of the thioredoxin system in photosynthetic Paulinella species.

Curr Biol 2021 Apr;31(7):R328-R329

Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Korea. Electronic address:

Redox regulation allows phytoplankton to monitor and stabilize metabolic pathways under changing conditions. In plastids, the thioredoxin (TRX) system is linked to photosynthetic electron transport and fine tuning of metabolic pathways to fluctuating light levels. Expansion of the number of redox signal transmitters and their protein targets, as seen in plants, is believed to increase cell robustness. Read More

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Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.

Cancer Cell 2021 Apr;39(4):566-579.e7

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institute of Health, Rockville, MD 20850, USA; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Small cell neuroendocrine cancers (SCNCs) are recalcitrant cancers arising from diverse primary sites that lack effective treatments. Using chemical genetic screens, we identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppresses genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC). In a proof-of-concept study, we combined M6620 (berzosertib), first-in-class ATR inhibitor, and TOP1 inhibitor topotecan in patients with relapsed SCNCs. Read More

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Early stem cell aging in the mature brain.

Cell Stem Cell 2021 Apr 7. Epub 2021 Apr 7.

Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; USC Davis School - Buck Institute Graduate Program in the Biology of Aging, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Program, W. M. Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90033, USA; Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA. Electronic address:

Stem cell dysfunction drives many age-related disorders. Identifying mechanisms that initially compromise stem cell behavior represent early targets to promote tissue function later in life. Here, we pinpoint multiple factors that disrupt neural stem cell (NSC) behavior in the adult hippocampus. Read More

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Distinct circuits in rat central amygdala for defensive behaviors evoked by socially signaled imminent versus remote danger.

Curr Biol 2021 Apr 7. Epub 2021 Apr 7.

Laboratory of Emotions Neurobiology, BRAINCITY-Centre of Excellence for Neural Plasticity and Brain Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. Electronic address:

Animals display a rich repertoire of defensive responses adequate to the threat proximity. In social species, these reactions can be additionally influenced by the behavior of fearful conspecifics. However, the majority of neuroscientific studies on socially triggered defensive responses focuses on one type of behavior, freezing. Read More

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Two modes of PRC1-mediated mechanical resistance to kinesin-driven microtubule network disruption.

Curr Biol 2021 Apr 6. Epub 2021 Apr 6.

Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address:

The proper organization of the microtubule-based spindle during cell division requires the collective activity of many different proteins. These include non-motor microtubule-associated proteins (MAPs), whose functions include crosslinking microtubules to regulate filament sliding rates and assemble microtubule arrays. One such protein is PRC1, an essential MAP that has been shown to preferentially crosslink overlapping antiparallel microtubules at the spindle midzone. Read More

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Impact of chromatin context on Cas9-induced DNA double-strand break repair pathway balance.

Mol Cell 2021 Apr 6. Epub 2021 Apr 6.

Oncode Institute, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands; Department of Cell Biology, Erasmus University Medical Centre, 3015 CN, Rotterdam, the Netherlands. Electronic address:

DNA double-strand break (DSB) repair is mediated by multiple pathways. It is thought that the local chromatin context affects the pathway choice, but the underlying principles are poorly understood. Using a multiplexed reporter assay in combination with Cas9 cutting, we systematically measure the relative activities of three DSB repair pathways as a function of chromatin context in >1,000 genomic locations. Read More

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Serial intravital imaging captures dynamic and functional endothelial remodeling with single-cell resolution.

JCI Insight 2021 Apr 13. Epub 2021 Apr 13.

Department of Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America.

Endothelial cells are important in the maintenance of healthy blood vessels and in the development of vascular diseases. However, the origin and dynamics of endothelial precursors and remodeling at the single-cell level have been difficult to study in vivo due to technical limitations. We aimed to develop a direct visual approach to track the fate and function of single endothelial cells over several days-weeks in the same vascular bed in vivo using multiphoton microscopy (MPM) of transgenic Cdh5-Confetti mice and the kidney glomerulus as a model. Read More

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Science: priceless, but costly.

Authors:
Marta Gabryelska

Mol Biol Cell 2021 Apr;32(8):635-637

College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, 2052 South Australia, Australia.

Working as a researcher is very satisfying. However, it comes with a price. This is a story about growing up as a scientist in the field of molecular biology. Read More

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Control the Neural Stem Cell Fate with Biohybrid Piezoelectrical Magnetite Micromotors.

Nano Lett 2021 Apr 13. Epub 2021 Apr 13.

School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

Inducing neural stem cells to differentiate and replace degenerated functional neurons represents the most promising approach for neural degenerative diseases including Parkinson's disease, Alzheimer's disease, etc. While diverse strategies have been proposed in recent years, most of these are hindered due to uncontrollable cell fate and device invasiveness. Here, we report a minimally invasive micromotor platform with biodegradable helical () as the framework and superparamagnetic FeO nanoparticles/piezoelectric BaTiO nanoparticles as the built-in function units. Read More

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Systematic Merging of Nonfullerene Acceptor π-Extension and Tetrafluorination Strategies Affords Polymer Solar Cells with >16% Efficiency.

J Am Chem Soc 2021 Apr 13. Epub 2021 Apr 13.

Department of Chemistry, the Center for Light Energy Activated Redox Processes (LEAP), and the Materials Research Center (MRC), Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

The end-capping group (EG) is the essential electron-withdrawing component of nonfullerene acceptors (NFAs) in bulk heterojunction (BHJ) organic solar cells (OSCs). To systematically probe the impact of two frequent EG functionalization strategies, π-extension and halogenation, in A-DAD-A type NFAs, we synthesized and characterized four such NFAs: , , , and . To assess the relative importance of these strategies, we contrast these NFAs with the baseline acceptors, and . Read More

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Computational Saturation Screen Reveals the Landscape of Mutations in Human Fumarate Hydratase.

J Chem Inf Model 2021 Apr 13. Epub 2021 Apr 13.

Department of Medical Physics and Biomedical Engineering, UCL, London WC1E 6BT, U.K.

Single amino acid substitutions within protein structures often manifest with clinical conditions in humans. The mutation of a single amino can significantly alter protein folding and stability, or change protein dynamics to influence function. The chemical engineering field has developed a large toolset for predicting the influence of point mutations with the aim of guiding the design of improved and more stable proteins. Read More

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Core-Shell Tecto Dendrimers Enable Enhanced Tumor MR Imaging through an Amplified EPR Effect.

Biomacromolecules 2021 Apr 13. Epub 2021 Apr 13.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.

Development of nanoplatforms that can amplify the passive tumor targeting effect based on enhanced permeability and retention (EPR) effect is crucial for precision cancer nanomedicine applications. Herein, we present the development of core-shell tecto dendrimers (CSTDs) as a platform for enhanced tumor magnetic resonance (MR) imaging through an amplified EPR effect. In this work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were decorated with β-cyclodextrin (CD) and then assembled with G3 PAMAM dendrimers premodified with adamantane (Ad) via supramolecular recognition of CD and Ad. Read More

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Presentation, Management and Outcomes of Pediatric Pulmonary Embolus: A Retrospective Review.

Pediatr Emerg Care 2021 Apr 9. Epub 2021 Apr 9.

From the *Department of Pediatrics, Massachusetts General Hospital for Children †Department of Medicine, Massachusetts General Hospital, Boston MA.

Objectives: To review the presentation, management, and outcomes of pediatric pulmonary embolism (PE) patients treated at a single institution over 10 years to determine whether laboratory findings and clinical presentation predict disease severity.

Methods: We performed a retrospective chart review of patients treated for PE in a 14-bed pediatric intensive care unit from January 1, 2008, to December 31, 2018. Associations between clot burden and disease severity, clinical risk factors (body mass index, recent hospitalization, estrogen use), clinical presentation (heart rate, oxygen saturation), and laboratory values (white blood cell count, D-Dimer, troponin, proBNP) were performed using Student t test, χ tests, and 1-way analysis of variance. Read More

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Diagnostic utility of rapid on-site evaluation of endobronchial ultrasound-guided transbronchial needle aspiration samples: A study in a region of high tuberculosis burden.

Cytopathology 2021 Apr 13. Epub 2021 Apr 13.

Department of Pathology, Dr. Ram Manohar Lohia Hospital & ABVIMS, New Delhi, India.

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool for precise diagnosis of thoracic lesions. However, the procedure sometimes has a poor yield. Rapid on-site evaluation (ROSE) in EBUS-TBNA has been shown to be helpful to improve its diagnostic yield and minimise the need for repeat procedures. Read More

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LGR6 marks nephron progenitor cells.

Dev Dyn 2021 Apr 13. Epub 2021 Apr 13.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Background: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multi-step process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists. Read More

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The emergence of a complex pore-canal system in the dermal skeleton of Tremataspis (Osteostraci).

J Morphol 2021 Apr 13. Epub 2021 Apr 13.

Department of Organismal Biology, Uppsala University, Uppsala, Sweden.

Thyestiids are a group of osteostracans (sister-group to jawed vertebrates) ranging in time from the early Silurian to Middle Devonian. Tremataspis is unique among thyestiids in having a continuous mesodentine and enameloid cover on its dermal elements, and an embedded pore-canal system divided into lower and upper parts by a perforated septum. The origin of this upper mesh canal system and its potential homology to similar canal systems of other osteostracans has remained a matter of debate. Read More

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Stimulation of Variant Forms of the Mitochondrial DNA Helicase Twinkle by the Mitochondrial Single-Stranded DNA-Binding Protein.

Methods Mol Biol 2021 ;2281:313-322

Departamento de Tecnologia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista "Júlio de Mesquita Filho", Jaboticabal, SP, Brazil.

Defects in mitochondrial DNA (mtDNA) maintenance may lead to disturbances in mitochondrial homeostasis and energy production in eukaryotic cells, causing diseases. During mtDNA replication, the mitochondrial single-stranded DNA-binding protein (mtSSB) stabilizes and protects the exposed single-stranded mtDNA from nucleolysis; perhaps more importantly, it appears to coordinate the actions of both the replicative mtDNA helicase Twinkle and DNA polymerase gamma at the replication fork. Here, we describe a helicase stimulation protocol to test in vitro the functional interaction between mtSSB and variant forms of Twinkle. Read More

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January 2021

Selective Suppression of Endogenous Gene Expression Using RNAi in Drosophila Schneider S2 Cells.

Methods Mol Biol 2021 ;2281:303-312

Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

RNA interference (RNAi) is a posttranscriptional gene silencing method that is triggered by double-stranded RNA (dsRNA). RNAi is used to inactivate genes of interest and provides a genetic tool for loss-of-function studies in a variety of organisms.I have used this method to reveal the physiological roles of a number of endogenous proteins involved in mitochondrial DNA metabolism in Schneider cells, including the mitochondrial single-stranded DNA-binding protein. Read More

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January 2021

Optical Tweezers to Investigate the Structure and Energetics of Single-Stranded DNA-Binding Protein-DNA Complexes.

Methods Mol Biol 2021 ;2281:273-288

Instituto Madrileño de Estudios Avanzados en Nanociencia, IMDEA Nanociencia, Madrid, Spain.

Optical tweezers enable the isolation and mechanical manipulation of individual nucleoprotein complexes. Here, we describe how to use this technique to interrogate the mechanical properties of individual protein-DNA complexes and extract information about their overall structural organization. Read More

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January 2021

Quantifying the Affinity of Trypanosoma cruzi RPA-1 to the Single-Stranded DNA Overhang of the Telomere Using Surface Plasmon Resonance.

Methods Mol Biol 2021 ;2281:217-228

Cell Cycle Laboratory, Butantan Institute, São Paulo, SP, Brazil.

Surface plasmon resonance (SPR) biosensors provide real-time binding affinity measurements between a pair of biomolecules, characterizing its interaction dynamics. An example of Trypanosoma cruzi's RPA-1 and a single-stranded DNA telomere sequence is presented with detailed guidelines and fundamentals for SPR technology. Read More

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January 2021

In Vivo Binding of Single-Stranded DNA-Binding Protein to Stalled Replication Fork Helicases.

Methods Mol Biol 2021 ;2281:81-91

Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Understanding protein-protein interactions is key to unraveling protein function in vivo. Here we describe a dual/triple-plasmid system that enables co-expression of two, or three, recombinant proteins harboring different affinity tags in the same Escherichia coli cell. This novel protein expression system provides a platform to understand protein-protein interactions and enables researchers to study protein complex formation and in vivo localization. Read More

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January 2021

Single-Stranded DNA-Binding Proteins in the Archaea.

Methods Mol Biol 2021 ;2281:23-47

Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, UK.

Single-stranded (ss) DNA-binding proteins are found in all three domains of life where they play vital roles in nearly all aspects of DNA metabolism by binding to and stabilizing exposed ssDNA and acting as platforms onto which DNA-processing activities can assemble. The ssDNA-binding factors SSB and RPA are extremely well conserved across bacteria and eukaryotes, respectively, and comprise one or more OB-fold ssDNA-binding domains. In the third domain of life, the archaea, multiple types of ssDNA-binding protein are found with a variety of domain architectures and subunit compositions, with OB-fold ssDNA-binding domains being a characteristic of most, but not all. Read More

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January 2021