Structural mechanism of HP1⍺-dependent transcriptional repression and chromatin compaction.

Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. Here, we present the cryoelectron microscopy (cryo-EM) structure of an HP1α dimer bound to an H2A.

Structural mechanism of HP1α-dependent transcriptional repression and chromatin compaction.

Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. In this study, we employed a multidisciplinary approach to unravel the interactions between human HP1α and nucleosomes.

RNA polymerase drives ribonucleotide excision DNA repair in E. coli.

Ribonuclease HII (RNaseHII) is the principal enzyme that removes misincorporated ribonucleoside monophosphates (rNMPs) from genomic DNA. Here, we present structural, biochemical, and genetic evidence demonstrating that ribonucleotide excision repair (RER) is directly coupled to transcription. Affinity pull-downs and mass-spectrometry-assisted mapping of in cellulo inter-protein cross-linking reveal the majority of RNaseHII molecules interacting with RNA polymerase (RNAP) in E.

Shelterin is a dimeric complex with extensive structural heterogeneity.

Human shelterin is a six-subunit complex-composed of TRF1, TRF2, Rap1, TIN2, TPP1, and POT1-that binds telomeres, protects them from the DNA-damage response, and regulates the maintenance of telomeric DNA. Although high-resolution structures have been generated of the individual structured domains within shelterin, the architecture and stoichiometry of the full complex are currently unknown. Here, we report the purification of shelterin subcomplexes and reconstitution of the entire complex using full-length, recombinant subunits.

Cryo-EM structure of the human CST-Polα/primase complex in a recruitment state.

The CST-Polα/primase complex is essential for telomere maintenance and functions to counteract resection at double-strand breaks. We report a 4.6-Å resolution cryo-EM structure of human CST-Polα/primase, captured prior to catalysis in a recruitment state stabilized by chemical cross-linking.

Crucial role and mechanism of transcription-coupled DNA repair in bacteria.

Transcription-coupled DNA repair (TCR) is presumed to be a minor sub-pathway of nucleotide excision repair (NER) in bacteria. Global genomic repair is thought to perform the bulk of repair independently of transcription. TCR is also believed to be mediated exclusively by Mfd-a DNA translocase of a marginal NER phenotype.

Rho-dependent transcription termination: a revisionist view.

Rho is a hexameric bacterial RNA helicase, which became a paradigm of factor-dependent transcription termination. The broadly accepted ("textbook") model posits a series of steps, wherein Rho first binds C-rich () sites on nascent RNA, uses its ATP-dependent translocase activity to catch up with RNA polymerase (RNAP), and either pulls the transcript from the elongation complex or pushes RNAP forward, thus terminating transcription. However, this appealingly simple mechano-chemical model lacks a biological realism and is increasingly at odds with genetic and biochemical data.

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides.

The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites, and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation in bacterial cells) Nsp12 exists in an inactive state in which NiRAN-RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or nucleoside triphosphates (NTPs) partially rescue RdRp activity.

Allosteric activation of SARS-CoV-2 RdRp by remdesivir triphosphate and other phosphorylated nucleotides.

Unlabelled: The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation) Nsp12 exists in inactive state in which NiRAN/RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or NTPs partially rescue RdRp activity.

Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction.

Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin.

[History of surgical and non-surgical tracheal intubation].

Anesthesiologist daily encounters the need for maintaining an airway patency. This manuscript is devoted to the development of this technique from ancient times to the present. Three areas including tracheostomy, endoscopy and tracheal intubation are comprehensively described.

Pre-termination Transcription Complex: Structure and Function.

Rho is a general transcription termination factor playing essential roles in RNA polymerase (RNAP) recycling, gene regulation, and genomic stability in most bacteria. Traditional models of transcription termination postulate that hexameric Rho loads onto RNA prior to contacting RNAP and then translocates along the transcript in pursuit of the moving RNAP to pull RNA from it. Here, we report the cryoelectron microscopy (cryo-EM) structures of two termination process intermediates.

Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex.

Misfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome. ERAD-L is mediated by the Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, and Yos9), but the mechanism of retrotranslocation remains mysterious. Here, we report a structure of the active Hrd1 complex, as determined by cryo-electron microscopy analysis of two subcomplexes.

Towards the unified principles of transcription termination.

Discovery of the role of bacterial RNase J1 in termination of transcription suggests common allosteric principles and mechanistic congruency of termination between bacteria and eukaryotes, in which an unrelated RNase Xrn2/Rat1 plays a similar role.

[Practical aspects of sedation in dentistry].

In modern dental practice, the use of sedation to eliminate the fear and anxiety of the patient has become frequent. Unfortunately, according to the legislation, the concept of sedation is inseparable from anesthesia and it can only be performed by an anesthesiologist in a group or Department of Anesthesiology and Resuscitation. The article is devoted to a detailed comprehensive review of sedation in dental and surgical interventions in the maxillofacial area.

The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach.

The unique membrane composition of cilia is maintained by a diffusion barrier at the transition zone that is breached when the BBSome escorts signaling receptors out of cilia. Understanding how the BBSome removes proteins from cilia has been hampered by a lack of structural information. Here, we present a nearly complete Cα model of BBSome purified from cow retina.

Design of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer.

New chemical inhibitors of protein-protein interactions are needed to propel advances in molecular pharmacology. Peptoids are peptidomimetic oligomers with the capability to inhibit protein-protein interactions by mimicking protein secondary structure motifs. Here we report the in silico design of a macrocycle primarily composed of peptoid subunits that targets the β-catenin:TCF interaction.

Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4.

Many polyubiquitinated proteins are extracted from membranes or complexes by the conserved ATPase Cdc48 (in yeast; p97 or VCP in mammals) before proteasomal degradation. Each Cdc48 hexamer contains two stacked ATPase rings (D1 and D2) and six N-terminal (N) domains. Cdc48 binds various cofactors, including the Ufd1-Npl4 heterodimer.

Reading of the non-template DNA by transcription elongation factors.

Unlike transcription initiation and termination, which have easily discernable signals, such as promoters and terminators, elongation is regulated through a dynamic network involving RNA/DNA pause signals and states-rather than sequence-specific protein interactions. A report by Nedialkov et al. () provides experimental evidence for sequence-specific recruitment of elongation factor RfaH to transcribing RNA polymerase (RNAP) and outlines the mechanism of gene expression regulation by restraint ('locking') of the DNA non-template strand.

[THE CHOICE OF TRACHEAL INTUBATION METHOD IN RECONSTRUCTIVE MAXILLO-FACIAL SURGERY WITH DIFFICULT AIRWAYS.].

Background: The development of modern video - and endoscopic equipment allows for revision and adjust to modern protocols for maintaining patency of the difficult airway, especially in maxillofacial or ENT -surgery.

The Purpose Of The Study: Comparison the efficacy ofvarious methods of maintaining the airway patency in the practice of reconstructive maxillofacial surgery.

Materials And Methods: 89 patients, who were divided into 4 groups, were examined.

[Laparoscopic decompression of celiac trunk in children].

Material And Methods: For the period 2013-2016 four patients were treated at the Filatov Children's City Clinical Hospital #13. There were 2 children aged 14 years and 2 children aged 17 years. All patients have been diagnosed via anamnesis, complaints, pulse-wave doppler sonography, contrast-enhanced MDCT and angiography.

Structure of RNA polymerase bound to ribosomal 30S subunit.

In bacteria, mRNA transcription and translation are coupled to coordinate optimal gene expression and maintain genome stability. Coupling is thought to involve direct interactions between RNA polymerase (RNAP) and the translational machinery. We present cryo-EM structures of RNAP core bound to the small ribosomal 30S subunit.

[INFUSION THERAPY IN RECONSTRUCTIVE MAXILLOFACIAL SURGERY].

Unlabelled: Restricted infusion strategy in combination with antifibrinolytic agents such as aprotinin and tranexamic acid is effective for blood saving in maxillofacial surgery. But reduction of infusion volume can lead to intraoperative hypovolemia. The goal of this study was to assess compensative effect of different regimes of infusion therapy and antifibrinolytics on intraoperative volume status and electrolyte balance in reconstructive maxillofacial surgery.

Ratcheting of RNA polymerase toward structural principles of RNA polymerase operations.

RNA polymerase (RNAP) performs various tasks during transcription by changing its conformational states, which are gradually becoming clarified. A recent study focusing on the conformational transition of RNAP between the ratcheted and tight forms illuminated the structural principles underlying its functional operations.