Smaranda Willcox
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View article: Apolipoprotein E (APOE) regulates the transport of monosialotetrahexosylganglioside (GM1)
Apolipoprotein E (APOE) regulates the transport of monosialotetrahexosylganglioside (GM1) Open
Apolipoprotein E (APOE) is a key lipid transporter involved in the trafficking and clearance. The ε4 allele of APOE (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), and certain lipids are closely linked…
View article: Linear DNA-driven recombination in mammalian mitochondria
Linear DNA-driven recombination in mammalian mitochondria Open
Mitochondrial DNA (mtDNA) recombination in animals has remained enigmatic due to its uniparental inheritance and subsequent homoplasmic state, which excludes the biological need for genetic recombination, as well as limits tools to study i…
View article: CD81 fusion alters SARS-CoV-2 Spike trafficking
CD81 fusion alters SARS-CoV-2 Spike trafficking Open
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the biggest public health crises in recent history. Many expect future coronavirus introductions into the human population. Hence, it is essential to understa…
View article: Large‐scale heparin‐based bind‐and‐elute chromatography identifies two biologically distinct populations of extracellular vesicles
Large‐scale heparin‐based bind‐and‐elute chromatography identifies two biologically distinct populations of extracellular vesicles Open
Purifying extracellular vesicles (EVs) has been challenging because EVs are heterogeneous in cargo yet share similar sizes and densities. Most surface marker‐based affinity separation methods are limited to research or diagnostic scales. W…
View article: Peptide Amphiphile Supramolecular Nanofibers Designed to Target Abdominal Aortic Aneurysms
Peptide Amphiphile Supramolecular Nanofibers Designed to Target Abdominal Aortic Aneurysms Open
An abdominal aortic aneurysm (AAA) is a localized dilation of the aorta located in the abdomen that poses a severe risk of death when ruptured. The cause of AAA is not fully understood, but degradation of medial elastin due to elastolytic …
View article: Imaging of surface microdomains on individual extracellular vesicles in 3‐D
Imaging of surface microdomains on individual extracellular vesicles in 3‐D Open
Extracellular vesicles (EVs) are secreted from all cell types and are intimately involved in tissue homeostasis. They are being explored as vaccine and gene therapy platforms, as well as potential biomarkers. As their size is below the dif…
View article: Differential Single-stranded DNA Binding Properties of the Paralogous SsbA and SsbB Proteins from Streptococcus pneumoniae
Differential Single-stranded DNA Binding Properties of the Paralogous SsbA and SsbB Proteins from Streptococcus pneumoniae Open
The naturally transformable Gram-positive bacterium Streptococcus pneumoniae has two single-stranded DNA-binding (SSB) proteins, designated SsbA and SsbB. The SsbA protein is similar in size to the well characterized SSB protein from Esche…
View article: A Single-stranded DNA-binding Protein of Bacteriophage T7 Defective in DNA Annealing
A Single-stranded DNA-binding Protein of Bacteriophage T7 Defective in DNA Annealing Open
The annealing of complementary strands of DNA is a vital step during the process of DNA replication, recombination, and repair. In bacteriophage T7-infected cells, the product of viral gene 2.5, a single-stranded DNA-binding protein, perfo…
View article: The Basic Domain of TRF2 Directs Binding to DNA Junctions Irrespective of the Presence of TTAGGG Repeats
The Basic Domain of TRF2 Directs Binding to DNA Junctions Irrespective of the Presence of TTAGGG Repeats Open
The replication of long tracts of telomeric repeats may require specific factors to avoid fork regression (Fouché, N., Ozgür, S., Roy, D., and Griffith, J. (2006) Nucleic Acids Res., in press). Here we show that TRF2 binds to model replica…
View article: Taz1 Binding to a Fission Yeast Model Telomere: FORMATION OF TELOMERIC LOOPS AND HIGHER ORDER STRUCTURES
Taz1 Binding to a Fission Yeast Model Telomere: FORMATION OF TELOMERIC LOOPS AND HIGHER ORDER STRUCTURES Open
Similar to its human homologues TRF1 and TRF2, fission yeast Taz1 protein is a component of telomeric chromatin regulating proper telomere maintenance. As mammalian TRF1 and TRF2 proteins have been shown to directly bind telomeric DNA to f…
View article: Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks
Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks Open
Analysis of human heart mitochondrial DNA (mtDNA) by electron microscopy and agarose gel electrophoresis revealed a complete absence of the θ-type replication intermediates seen abundantly in mtDNA from all other tissues. Instead only Y- a…
View article: Synergism of the Two Myb Domains of Tay1 Protein Results in High Affinity Binding to Telomeres
Synergism of the Two Myb Domains of Tay1 Protein Results in High Affinity Binding to Telomeres Open
Double-stranded regions of the telomeres are recognized by proteins containing Myb-like domains conferring specificity toward telomeric repeats. Although biochemical and structural studies revealed basic molecular principles involved in DN…
View article: DNA Replication Catalyzed by Herpes Simplex Virus Type 1 Proteins Reveals Trombone Loops at the Fork
DNA Replication Catalyzed by Herpes Simplex Virus Type 1 Proteins Reveals Trombone Loops at the Fork Open
Using purified replication factors encoded by herpes simplex virus type 1 and a 70-base minicircle template, we obtained robust DNA synthesis with leading strand products of >20,000 nucleotides and lagging strand fragments from 600 to 9,00…
View article: Tay1 Protein, a Novel Telomere Binding Factor from Yarrowia lipolytica
Tay1 Protein, a Novel Telomere Binding Factor from Yarrowia lipolytica Open
Inspection of the complete genome of the yeast Yarrowia lipolytica for the presence of genes encoding homologues of known telomere-binding proteins surprisingly revealed no counterparts of typical yeast Myb domain-containing telomeric fact…
View article: A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans
A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans Open
Mitochondrial DNA (mtDNA) encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s) of its synthesis remain hotly debated…
View article: Improved methods for creating migratable Holliday junction substrates
Improved methods for creating migratable Holliday junction substrates Open
Previously, we published a method for creating a novel DNA substrate, the double Holliday junction substrate. This substrate contains two Holliday junctions that are mobile, topologically constrained and separated by a distance comparable …
View article: Mammalian Mitochondrial DNA Replication Intermediates Are Essentially Duplex but Contain Extensive Tracts of RNA/DNA Hybrid
Mammalian Mitochondrial DNA Replication Intermediates Are Essentially Duplex but Contain Extensive Tracts of RNA/DNA Hybrid Open
We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mtDNA replication intermediates (mtRIs) are essentially duplex throughout their length, but contain ext…
View article: Catalysis of Strand Exchange by the HSV-1 UL12 and ICP8 Proteins: Potent ICP8 Recombinase Activity is Revealed upon Resection of dsDNA Substrate by Nuclease
Catalysis of Strand Exchange by the HSV-1 UL12 and ICP8 Proteins: Potent ICP8 Recombinase Activity is Revealed upon Resection of dsDNA Substrate by Nuclease Open
The replication of herpes simplex virus type 1 (HSV-1) is associated with a high degree of homologous recombination, which is likely to be mediated, in part, by HSV-1-encoded proteins. We have previously shown that the HSV-1 encoded ICP8 p…
View article: Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity
Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity Open
MicroDNAs are <400-base extrachromosomal circles found in mammalian cells. Tens of thousands of microDNAs have been found in all tissue types, including sperm. MicroDNAs arise preferentially from areas with high gene density, GC content, a…
View article: Evolution of Telomeres in Schizosaccharomyces pombe and Its Possible Relationship to the Diversification of Telomere Binding Proteins
Evolution of Telomeres in Schizosaccharomyces pombe and Its Possible Relationship to the Diversification of Telomere Binding Proteins Open
Telomeres of nuclear chromosomes are usually composed of an array of tandemly repeated sequences that are recognized by specific Myb domain containing DNA-binding proteins (telomere-binding proteins, TBPs). Whereas in many eukaryotes the l…
View article: Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops
Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops Open
The formation of DNA loops at chromosome ends (t-loops) and the transcription of telomeres producing G-rich RNA (TERRA) represent two central features of telomeres. To explore a possible link between them we employed artificial human telom…
View article: Yeast mitochondrial HMG proteins: DNA-binding properties of the most evolutionarily divergent component of mitochondrial nucleoids
Yeast mitochondrial HMG proteins: DNA-binding properties of the most evolutionarily divergent component of mitochondrial nucleoids Open
Comparative biochemical analysis of mtHMG proteins from distantly related yeast species revealed that they exhibit a preference for recombination/replication intermediates. We discuss how these biochemical characteristics relate to the rol…
View article: Telomere Recognition and Assembly Mechanism of Mammalian Shelterin
Telomere Recognition and Assembly Mechanism of Mammalian Shelterin Open
Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembl…
View article: A New View of the T-Loop Junction: Implications for Self-Primed Telomere Extension, Expansion of Disease-Related Nucleotide Repeat Blocks, and Telomere Evolution
A New View of the T-Loop Junction: Implications for Self-Primed Telomere Extension, Expansion of Disease-Related Nucleotide Repeat Blocks, and Telomere Evolution Open
Telomere loops (t-loops) are formed at the ends of chromosomes in species ranging from humans to worms, plants, and with genetic manipulation, some yeast. Recent in vitro studies demonstrated that transcription of telomeric DNA leads to hi…
View article: Commentary: Single-stranded telomere-binding protein employs a dual rheostat for binding affinity and specificity that drives function
Commentary: Single-stranded telomere-binding protein employs a dual rheostat for binding affinity and specificity that drives function Open
GENERAL COMMENTARY article Front. Genet., 15 January 2019Sec. Genetics of Aging Volume 9 - 2018 | https://doi.org/10.3389/fgene.2018.00742
View article: Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops
Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops Open
The formation of DNA loops at chromosome ends (t-loops) and the transcription of telomeres producing G-rich RNA (TERRA) represent two central features of telomeres. To explore a possible link between them we employed artificial human telom…