Smita S. Patel
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View article: Torsion is a dynamic regulator of DNA replication stalling and reactivation
Torsion is a dynamic regulator of DNA replication stalling and reactivation Open
DNA’s helical structure necessitates replisome rotation relative to DNA during replication, creating inevitable topological challenges. How replication generates and overcomes torsional stress remains unclear. Here, we developed a high-res…
View article: Large-scale single-molecule analysis of tau proteoforms
Large-scale single-molecule analysis of tau proteoforms Open
Proteins exist as diverse proteoforms resulting from a combination of genetic variation, alternative splicing, and post-translational modifications. Current methods struggle to capture this complexity at the single-molecule level. Here we …
View article: An Emerging Global Threat of Mycotic Keratitis Caused by Uncommon Fungal Species: A Systematic Review and Meta-Analysis
An Emerging Global Threat of Mycotic Keratitis Caused by Uncommon Fungal Species: A Systematic Review and Meta-Analysis Open
This review catalogues the epidemiological, clinical, and morphological traits of rare fungi implicated in atypical MK and also provides a global prevalence estimate. Further, it emphasizes the role of implementation of specialized diagnos…
View article: Human mitochondrial RNA polymerase structures reveal transcription start-site and slippage mechanism
Human mitochondrial RNA polymerase structures reveal transcription start-site and slippage mechanism Open
SUMMARY Human mitochondrial RNA polymerase (POLRMT) and protein factors TFAM and TFB2M assemble on mitochondrial DNA promoters to initiate promoter-specific transcription. We present cryo-EM structures of two initiation complexes, IC3 and …
View article: Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation
Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation Open
The inherent helical structure of DNA dictates that a replisome must rotate relative to DNA during replication, presenting inevitable topological challenges to replication. However, little is known about how the replisome progresses agains…
View article: DNA Polymerase Locks Replication Fork Under Stress
DNA Polymerase Locks Replication Fork Under Stress Open
Replication of DNA requires the parental DNA to be unwound to allow the genetic information to be faithfully duplicated by the replisome. While this function is usually shared by a host of proteins in the replisome, notably DNA polymerase …
View article: Lipid Trajectories Improve Risk Models for Alzheimer’s Disease and Mild Cognitive Impairment
Lipid Trajectories Improve Risk Models for Alzheimer’s Disease and Mild Cognitive Impairment Open
To assess the relationship between lipids and cognitive dysfunction, we retrospectively analyzed blood-lipid levels in clinically well-characterized individuals with stable mild cognitive impairment (MCI) or Alzheimer’s disease (AD) over t…
View article: Sequence-specific dynamic DNA bending explains mitochondrial TFAM’s dual role in DNA packaging and transcription initiation
Sequence-specific dynamic DNA bending explains mitochondrial TFAM’s dual role in DNA packaging and transcription initiation Open
Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand …
View article: Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA
Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA Open
The RIG-I-like receptors (RLRs), comprising retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), are pattern recognition receptors belonging to the D…
View article: The NS1 protein of influenza B virus binds 5’-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response
The NS1 protein of influenza B virus binds 5’-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response Open
Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non-structural protein 1 of influenza B virus…
View article: Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2
Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2 Open
The RIG-I family helicases, comprising RIG-I, MDA5 and LGP2, are cytoplasmic RNA sensors that trigger an antiviral immune response by specifically recognizing foreign RNAs. While LGP2 lacks the signaling domain necessary for immune activat…
View article: Twinkle-Catalyzed Toehold-Mediated DNA Strand Displacement Reaction
Twinkle-Catalyzed Toehold-Mediated DNA Strand Displacement Reaction Open
Strand exchange between homologous nucleic acid sequences is the basis for cellular DNA repair, recombination, and genome editing technologies. Specialized enzymes catalyze cellular strand exchange; however, the reaction occurs spontaneous…
View article: The NS1 protein of influenza B virus binds 5’-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response
The NS1 protein of influenza B virus binds 5’-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response Open
SUMMARY Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non- structural protein 1 of influenz…
View article: RIG-I recognizes metabolite-capped RNAs as signaling ligands
RIG-I recognizes metabolite-capped RNAs as signaling ligands Open
The innate immune receptor RIG-I recognizes 5′-triphosphate double-stranded RNAs (5′ PPP dsRNA) as pathogenic RNAs. Such RNA-ends are present in viral genomes and replication intermediates, and they activate the RIG-I signaling pathway to …
View article: Expression and Purification of Recombinant Human Mitochondrial RNA Polymerase (POLRMT) and the Initiation Factors TFAM and TFB2M
Expression and Purification of Recombinant Human Mitochondrial RNA Polymerase (POLRMT) and the Initiation Factors TFAM and TFB2M Open
Human mitochondrial DNA (mtDNA) encodes several components of oxidative phosphorylation responsible for the bulk of cellular energy production. The mtDNA is transcribed by a dedicated human mitochondrial RNA polymerase (POLRMT) that is str…
View article: The N-terminal domain of the human mitochondrial helicase Twinkle has DNA binding activity crucial for supporting processive DNA synthesis by Polymerase γ
The N-terminal domain of the human mitochondrial helicase Twinkle has DNA binding activity crucial for supporting processive DNA synthesis by Polymerase γ Open
Twinkle is the ring-shaped replicative helicase within the human mitochondria with high homology to bacteriophage T7 gp4 helicase-primase. Unlike many orthologs of Twinkle, the N-terminal domain (NTD) of human Twinkle has lost its primase …
View article: Commentary
Commentary Open
With continuing advancements in techniques and technology, cataract surgery has emerged as one of the most demanding procedures, though perfection seems an elusive goal. According to National Programme for Control of Blindness and Visual I…
View article: Yeast mtDNA transcription initiation in single nucleotide addition steps
Yeast mtDNA transcription initiation in single nucleotide addition steps Open
Transcription initiation catalyzed by the RNA polymerase is a multistep process involving promoter binding, transcription bubble formation, abortive RNA synthesis, and transition into elongation following promoter escape. We report cryo-EM…
View article: Yeast mtDNA transcription initiation in single nucleotide addition steps
Yeast mtDNA transcription initiation in single nucleotide addition steps Open
Transcription initiation catalyzed by the RNA polymerase is a multistep process involving promoter binding, transcription bubble formation, abortive RNA synthesis, and transition into elongation following promoter escape. We report cryo-EM…
View article: Unusual Exaggerated Inflammatory Response in Fuchs Uveitis
Unusual Exaggerated Inflammatory Response in Fuchs Uveitis Open
Objective: To report a case of Fuchs uveitis with an unusual exaggerated inflammatory response in the form of multifocal fibrin deposition. Case Report: Fuchs uveitis syndrome (FUS) has a characteristic clinical appearance but is frequentl…
View article: The intrinsically disordered CARDs‐Helicase linker in RIG‐I is a molecular gate for RNA proofreading
The intrinsically disordered CARDs‐Helicase linker in RIG‐I is a molecular gate for RNA proofreading Open
The innate immune receptor RIG-I provides a first line of defense against viral infections. Viral RNAs are recognized by RIG-I's C-terminal domain (CTD), but the RNA must engage the helicase domain to release the signaling CARD (Caspase Ac…
View article: Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device
Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device Open
Summary Proteins are the main structural and functional components of cells, and their dynamic regulation and post-translational modifications (PTMs) underlie cellular phenotypes. Next-generation DNA sequencing technologies have revolution…
View article: Commentary: High fidelity and cost-effective cataract surgery training system: Need of the hour
Commentary: High fidelity and cost-effective cataract surgery training system: Need of the hour Open
Cataract is the most common cause of avoidable blindness in the Indian population, particularly over the age of 50 years, rendering cataract surgery as one of the most commonly performed surgical procedures.[1] It is a complex surgical pro…
View article: RIG-I uses its intrinsically disordered CARDs-Helicase linker in RNA proofreading functions
RIG-I uses its intrinsically disordered CARDs-Helicase linker in RNA proofreading functions Open
The innate immune receptor RIG-I provides the first line of defense against viral infections. Viral RNAs are recognized by the C-terminal domain (CTD) of RIG-I, but the RNA must engage the helicase domain to release the signaling domain CA…