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1.
Nat Chem ; 14(3): 267-273, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35177786

RESUMO

Tailoring electron transfer dynamics across solid-liquid interfaces is fundamental to the interconversion of electrical and chemical energy. Stacking atomically thin layers with a small azimuthal misorientation to produce moiré superlattices enables the controlled engineering of electronic band structures and the formation of extremely flat electronic bands. Here, we report a strong twist-angle dependence of heterogeneous charge transfer kinetics at twisted bilayer graphene electrodes with the greatest enhancement observed near the 'magic angle' (~1.1°). This effect is driven by the angle-dependent tuning of moiré-derived flat bands that modulate electron transfer processes with the solution-phase redox couple. Combined experimental and computational analysis reveals that the variation in electrochemical activity with moiré angle is controlled by a structural relaxation of the moiré superlattice at twist angles of <2°, and 'topological defect' AA stacking regions, where flat bands are localized, produce a large anomalous local electrochemical enhancement that cannot be accounted for by the elevated local density of states alone.

2.
Phys Rev Lett ; 127(16): 166802, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723600

RESUMO

Layers of two-dimensional materials stacked with a small twist angle give rise to beating periodic patterns on a scale much larger than the original lattice, referred to as a "moiré superlattice." Here, we demonstrate a higher-order "moiré of moiré" superlattice in twisted trilayer graphene with two consecutive small twist angles. We report correlated insulating states near the half filling of the moiré of moiré superlattice at an extremely low carrier density (∼10^{10} cm^{-2}), near which we also report a zero-resistance transport behavior typically expected in a 2D superconductor. The full-occupancy (ν=-4 and ν=4) states are semimetallic and gapless, distinct from the twisted bilayer systems.

3.
Chem Sci ; 12(39): 12959-12970, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34745526

RESUMO

Controlled formation of catalytically-relevant states within crystals of complex metalloenzymes represents a significant challenge to structure-function studies. Here we show how electrochemical control over single crystals of [NiFe] hydrogenase 1 (Hyd1) from Escherichia coli makes it possible to navigate through the full array of active site states previously observed in solution. Electrochemical control is combined with synchrotron infrared microspectroscopy, which enables us to measure high signal-to-noise IR spectra in situ from a small area of crystal. The output reports on active site speciation via the vibrational stretching band positions of the endogenous CO and CN- ligands at the hydrogenase active site. Variation of pH further demonstrates how equilibria between catalytically-relevant protonation states can be deliberately perturbed in the crystals, generating a map of electrochemical potential and pH conditions which lead to enrichment of specific states. Comparison of in crystallo redox titrations with measurements in solution or of electrode-immobilised Hyd1 confirms the integrity of the proton transfer and redox environment around the active site of the enzyme in crystals. Slowed proton-transfer equilibria in the hydrogenase in crystallo reveals transitions which are only usually observable by ultrafast methods in solution. This study therefore demonstrates the possibilities of electrochemical control over single metalloenzyme crystals in stabilising specific states for further study, and extends mechanistic understanding of proton transfer during the [NiFe] hydrogenase catalytic cycle.

4.
Light Sci Appl ; 10(1): 157, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326315

RESUMO

We demonstrate a photonic analog of twisted bilayer graphene that has ultra-flat photonic bands and exhibits extreme slow-light behavior. Our twisted bilayer photonic device, which has an operating wavelength in the C-band of the telecom window, uses two crystalline silicon photonic crystal slabs separated by a methyl methacrylate tunneling layer. We numerically determine the magic angle using a finite-element method and the corresponding photonic band structure, which exhibits a flat band over the entire Brillouin zone. This flat band causes the group velocity to approach zero and introduces light localization, which enhances the electromagnetic field at the expense of bandwidth. Using our original plane-wave continuum model, we find that the photonic system has a larger band asymmetry. The band structure can easily be engineered by adjusting the device geometry, giving significant freedom in the design of devices. Our work provides a fundamental understanding of the photonic properties of twisted bilayer photonic crystals and opens the door to the nanoscale-based enhancement of nonlinear effects.

5.
Sci Rep ; 11(1): 10617, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34012108

RESUMO

Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/farmacologia , Antivirais/metabolismo , COVID-19/prevenção & controle , Engenharia de Proteínas/métodos , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antivirais/química , COVID-19/tratamento farmacológico , COVID-19/enzimologia , COVID-19/virologia , Linhagem Celular , Desenho de Fármacos , Haplorrinos , Humanos , Ligação Proteica , Elementos Estruturais de Proteínas , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
6.
Nat Mater ; 20(7): 956-963, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33859383

RESUMO

Van der Waals heteroepitaxy allows deterministic control over lattice mismatch or azimuthal orientation between atomic layers to produce long-wavelength superlattices. The resulting electronic phases depend critically on the superlattice periodicity and localized structural deformations that introduce disorder and strain. In this study we used Bragg interferometry to capture atomic displacement fields in twisted bilayer graphene with twist angles <2°. Nanoscale spatial fluctuations in twist angle and uniaxial heterostrain were statistically evaluated, revealing the prevalence of short-range disorder in moiré heterostructures. By quantitatively mapping strain tensor fields, we uncovered two regimes of structural relaxation and disentangled the electronic contributions of constituent rotation modes. Further, we found that applied heterostrain accumulates anisotropically in saddle-point regions, generating distinctive striped strain phases. Our results establish the reconstruction mechanics underpinning the twist-angle-dependent electronic behaviour of twisted bilayer graphene and provide a framework for directly visualizing structural relaxation, disorder and strain in moiré materials.

7.
Case Rep Anesthesiol ; 2021: 6679845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747571

RESUMO

Effective tocolysis is essential after fetal myelomeningocele repair and is associated with the development of pulmonary edema. The increased uterine activity in the immediate postoperative period is commonly treated with magnesium sulfate. However, other tocolytic agents such as nitroglycerine, nifedipine, indomethacin, terbutaline, and atosiban (outside the US) have also been used to combat uterine contractility. The ideal tocolytic regimen which balances the risks and benefits of in-utero surgery has yet to be determined. In this case report, we describe a unique case of fetal myelomeningocele repair complicated by maternal pulmonary edema and increased uterine activity resistant to magnesium sulfate therapy.

8.
Nat Commun ; 12(1): 242, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431846

RESUMO

The emerging field of twistronics, which harnesses the twist angle between two-dimensional materials, represents a promising route for the design of quantum materials, as the twist-angle-induced superlattices offer means to control topology and strong correlations. At the small twist limit, and particularly under strain, as atomic relaxation prevails, the emergent moiré superlattice encodes elusive insights into the local interlayer interaction. Here we introduce moiré metrology as a combined experiment-theory framework to probe the stacking energy landscape of bilayer structures at the 0.1 meV/atom scale, outperforming the gold-standard of quantum chemistry. Through studying the shapes of moiré domains with numerous nano-imaging techniques, and correlating with multi-scale modelling, we assess and refine first-principle models for the interlayer interaction. We document the prowess of moiré metrology for three representative twisted systems: bilayer graphene, double bilayer graphene and H-stacked MoSe2/WSe2. Moiré metrology establishes sought after experimental benchmarks for interlayer interaction, thus enabling accurate modelling of twisted multilayers.

9.
Biochim Biophys Acta Gen Subj ; 1864(12): 129730, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32926959

RESUMO

BACKGROUND: Human Exonuclease1 (hExo1) participates in the resection of DNA double-strand breaks by generating long 3'-single-stranded DNA overhangs, critical for homology-based DNA repair and activation of the ATR-dependent checkpoint. The C-terminal region is essential for modulating the activity of hExo1, containing numerous sites of post-translational modification and binding sites for partner proteins. METHODS: Analytical Ultracentrifugation (AUC), Dynamic Light Scattering (DLS), Circular Dichroism (CD) spectroscopy and enzymatic assays. RESULTS: AUC and DLS indicates the C-terminal region has a highly extended structure while CD suggest a tendency to adopt a novel left-handed ß-sheet structure, together implying the C-terminus may exhibit a transient fluctuating structure that could play a role in binding partner proteins known to regulate the activity of hExo1. Interaction with 14-3-3 protein has a cooperative inhibitory effect upon DNA resection activity, which indicates an allosteric transition occurs upon binding partner proteins. CONCLUSIONS: This study has uncovered that hExo1 consist of a folded N-terminal nuclease domain and a highly extended C-terminal region which is known to interact with partner proteins that regulates the activity of hExo1. A positively cooperative mechanism of binding allows for stringent control of hExo1 activity. Such a transition would coordinate the control of hExo1 by hExo1 regulators and hence allow careful coordination of the process of DNA end resection. SIGNIFICANCE: The assays presented herein could be readily adapted to rapidly identify and characterise the effects of modulators of the interaction between the 14-3-3 proteins and hExo1. It is conceivable that small molecule modulators of 14-3-3 s-hExo1 interaction may serve as effective chemosensitizers for cancer therapy.


Assuntos
Enzimas Reparadoras do DNA/metabolismo , Exodesoxirribonucleases/metabolismo , Proteínas 14-3-3/metabolismo , Regulação Alostérica , Enzimas Reparadoras do DNA/química , Exodesoxirribonucleases/química , Humanos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ligação Proteica , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas
10.
Fetal Diagn Ther ; 47(12): 918-926, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32906121

RESUMO

INTRODUCTION: Twin-to-twin transfusion syndrome affects monochorionic twin pregnancies and can result in fetal death. Endoscopic laser treatment remains a relatively infrequent procedure for this condition. This presents difficulties for maintaining proficiency and for training new personnel. OBJECTIVE: The dual mentoring program at our institution allows for continuous mentoring of new providers. We hypothesize that this approach stabilizes program proficiency despite the addition of new practitioners. METHODS: Query of the fetal treatment program database returned 146 cases of laser ablation between 2000 and 2019. Patient and pregnancy characteristics as well as operative time and outcomes were recorded. The learning curve-cumulative summation method and rolling averages were used to analyze outcomes. RESULTS: Overall survival was 69%, and survival of at least 1 twin was 89%. Mean operative time was 53.6 ± 20.9 min. Overall twin survival stabilized after the first 40 cases. Rolling averages for operative time decreased from 71 to 49 min for the most recent cases. These results were not affected by the introduction of new surgeons. CONCLUSIONS: Creative mentoring can maintain stable overall program outcomes despite changes in team composition. This training approach may be applicable to other rare procedures in fetal surgery.


Assuntos
Transfusão Feto-Fetal , Curva de Aprendizado , Feminino , Morte Fetal , Transfusão Feto-Fetal/cirurgia , Fetoscopia , Feto , Humanos , Gravidez , Resultado da Gravidez
11.
Phys Rev Lett ; 125(11): 116404, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32975975

RESUMO

We introduce twisted trilayer graphene (tTLG) with two independent twist angles as an ideal system for the precise tuning of the electronic interlayer coupling to maximize the effect of correlated behaviors. As established by experiment and theory in the related twisted bilayer graphene system, van Hove singularities (VHS) in the density of states can be used as a proxy of the tendency for correlated behaviors. To explore the evolution of VHS in the twist-angle phase space of tTLG, we present a general low-energy electronic structure model for any pair of twist angles. We show that the basis of the model has infinite dimensions even at a finite energy cutoff and that no Brillouin zone exists even in the continuum limit. Using this model, we demonstrate that the tTLG system exhibits a wide range of magic angles at which VHS merge and that the density of states has a sharp peak at the charge-neutrality point through two distinct mechanisms: the incommensurate perturbation of twisted bilayer graphene's flatbands or the equal hybridization between two bilayer moiré superlattices.

12.
IUCrJ ; 7(Pt 5): 901-912, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32939282

RESUMO

Cryogenic X-ray diffraction is a powerful tool for crystallographic studies on enzymes including oxygenases and oxidases. Amongst the benefits that cryo-conditions (usually employing a nitro-gen cryo-stream at 100 K) enable, is data collection of di-oxy-gen-sensitive samples. Although not strictly anaerobic, at low temperatures the vitreous ice conditions severely restrict O2 diffusion into and/or through the protein crystal. Cryo-conditions limit chemical reactivity, including reactions that require significant conformational changes. By contrast, data collection at room temperature imposes fewer restrictions on diffusion and reactivity; room-temperature serial methods are thus becoming common at synchrotrons and XFELs. However, maintaining an anaerobic environment for di-oxy-gen-dependent enzymes has not been explored for serial room-temperature data collection at synchrotron light sources. This work describes a methodology that employs an adaptation of the 'sheet-on-sheet' sample mount, which is suitable for the low-dose room-temperature data collection of anaerobic samples at synchrotron light sources. The method is characterized by easy sample preparation in an anaerobic glovebox, gentle handling of crystals, low sample consumption and preservation of a localized anaerobic environment over the timescale of the experiment (<5 min). The utility of the method is highlighted by studies with three X-ray-radiation-sensitive Fe(II)-containing model enzymes: the 2-oxoglutarate-dependent l-arginine hy-droxy-lase VioC and the DNA repair enzyme AlkB, as well as the oxidase isopenicillin N synthase (IPNS), which is involved in the biosynthesis of all penicillin and cephalosporin antibiotics.

13.
Nat Commun ; 11(1): 4209, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826888

RESUMO

Direct visualization of nanometer-scale properties of moiré superlattices in van der Waals heterostructure devices is a critically needed diagnostic tool for study of the electronic and optical phenomena induced by the periodic variation of atomic structure in these complex systems. Conventional imaging methods are destructive and insensitive to the buried device geometries, preventing practical inspection. Here we report a versatile scanning probe microscopy employing infrared light for imaging moiré superlattices of twisted bilayers graphene encapsulated by hexagonal boron nitride. We map the pattern using the scattering dynamics of phonon polaritons launched in hexagonal boron nitride capping layers via its interaction with the buried moiré superlattices. We explore the origin of the double-line features imaged and show the mechanism of the underlying effective phase change of the phonon polariton reflectance at domain walls. The nano-imaging tool developed provides a non-destructive analytical approach to elucidate the complex physics of moiré engineered heterostructures.

14.
J Chem Inf Model ; 60(7): 3457-3462, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32574067

RESUMO

Two-dimensional (2D) layered materials offer intriguing possibilities for novel physics and applications. Before any attempt at exploring the materials space in a systematic fashion, or combining insights from theory, computation, and experiment, a formal description of information about an assembly of arbitrary composition is required. Here, we introduce a domain-generic notation that is used to describe the space of 2D layered materials from monolayers to twisted assemblies of arbitrary composition, existent or not yet fabricated. The notation corresponds to a theoretical materials concept of stepwise assembly of layered structures using a sequence of rotation, vertical stacking, and other operations on individual 2D layers. Its scope is demonstrated with a number of example structures using common single-layer materials as building blocks. This work overall aims to contribute to the systematic codification, capture, and transfer of materials knowledge in the area of 2D layered materials.


Assuntos
Redes Locais , Nanotecnologia
15.
J Am Chem Soc ; 142(29): 12699-12707, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32579353

RESUMO

Hydrogenase-1 (Hyd-1) from E. coli poses a conundrum regarding the properties of electrocatalytic reversibility and associated bidirectionality now established for many redox enzymes. Its excellent H2-oxidizing activity begins only once a substantial overpotential is applied, and it cannot produce H2. A major reason for its unidirectional behavior is that the reduction potentials of its electron-relaying FeS clusters are too positive relative to the 2H+/H2 couple at neutral pH; consequently, electrons held within the enzyme lack the energy to drive H2 production. However, Hyd-1 is O2-tolerant and even functions in air. Changing a tyrosine (Y) or threonine (T), located on the protein surface within 10 Å of the distal [4Fe-4S] and medial [3Fe-4S] clusters, to cysteine (C), allows site-selective attachment of a silver nanocluster (AgNC), the reduced or photoexcited state of which is a powerful reductant. The AgNC provides a new additional redox site, capturing externally supplied electrons with sufficiently high energy to drive H2 production. Assemblies of Y'227C (or T'225C) with AgNCs/PMAA (PMAA = polymethyl acrylate templating several AgNC) are also electroactive for H2 production at a TiO2 electrode. A colloidal system for visible-light photo-H2 generation is made by building the hybrid enzyme into a heterostructure with TiO2 and graphitic carbon nitride (g-C3N4), the resulting scaffold promoting uptake of electrons excited at the AgNC. Each hydrogenase produces 40 molecules of H2 per second and sustains 20% activity in air.

16.
MAbs ; 12(1): 1752529, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32316838

RESUMO

The success of therapeutic antibodies is largely attributed for their exquisite specificity, homogeneity, and functionality. There is, however, a need to engineer antibodies to extend and enhance their potency. One parameter is functional affinity augmentation, since antibodies matured in vivo have a natural affinity threshold. Generation of multivalent antibodies is one option capable of surpassing this affinity threshold through increased avidity. In this study, we present a novel platform consisting of an array of multivalent antibody formats, termed Quads, generated using the self-assembling tetramerization domain from p53. We demonstrate the versatility of this tetramerization domain by engineering anti-tumor necrosis factor (TNF) Quads that exhibit major increases in binding potency and in neutralizing TNF-mediated cytotoxicity compared to parental anti-TNF molecules. Further, Quads are amenable to fusion with different binding domains, allowing generation of novel multivalent monospecific and bispecific formats. Quads are thus a novel group of molecules that can be engineered to yield potential therapeutics with novel modalities and potencies.


Assuntos
Anticorpos Biespecíficos/imunologia , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos/imunologia , Engenharia de Proteínas/métodos , Multimerização Proteica/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Antígenos CD20/genética , Antígenos CD20/imunologia , Antígenos CD20/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células HEK293 , Humanos , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/imunologia , Fragmentos de Imunoglobulinas/metabolismo , Camundongos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
17.
Nano Lett ; 20(5): 3030-3038, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32208724

RESUMO

Electrons in quantum materials exhibiting coexistence of dispersionless (flat) bands piercing dispersive (steep) bands give rise to strongly correlated phenomena and are associated with unconventional superconductivity. We show that in twisted sandwiched graphene (TSWG)-a three-layer van der Waals heterostructure with a twisted middle layer-steep Dirac cones can coexist with dramatic band flattening at the same energy scale, if twisted by 1.5°. This phenomenon is not stable in the simplified continuum models. The key result of this Letter is that the flat bands become stable only as a consequence of lattice relaxation processes included in our atomistic calculations. Further on, external fields can change the relative energy offset between the Dirac cone vertex and the flat bands and enhance band hybridization, which could permit controlling correlated phases. Our work establishes twisted sandwiched graphene as a new platform for research into strongly interacting two-dimensional quantum matter.

18.
J Obstet Gynaecol Can ; 42(2): 177-178, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31289012

RESUMO

BACKGROUND: Myelomeningocele (MMC) is the most frequent congenital abnormality of the central nervous system that leads to significant physical disabilities. Historically, treatment involved postnatal repair with management of the hydrocephalus with ventricular shunting. Animal and early human studies demonstrated the feasibility of fetal closure. The benefit of in-utero closure was debated until the results of the prospective randomized multicenter Management of Myelomeningocele Study (MOMS trial) were published, demonstrating a decreased need for shunting, reversal of hindbrain herniation, and better neurologic function in the prenatal repair group compared to postnatal repair. Fetal MMC closure has become a standard of care option for prenatally diagnosed spina bifida. The size of the spinal defect may require modification of the classic surgical technique requiring patching. CASE: This report describes a case of open fetal myelomeningocele repair, which required incorporation of a skin allograft. CONCLUSION: Large myelomeningocele defects may be successfully repaired with utilization of a skin allograft.


Assuntos
Meningomielocele/diagnóstico , Diagnóstico Pré-Natal , Adulto , Aloenxertos , Diagnóstico Diferencial , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/cirurgia , Humanos , Imageamento por Ressonância Magnética , Meningomielocele/diagnóstico por imagem , Meningomielocele/cirurgia , Gravidez , Resultado da Gravidez
19.
J Appl Crystallogr ; 52(Pt 6): 1385-1396, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31798361

RESUMO

Serial crystallography, at both synchrotron and X-ray free-electron laser light sources, is becoming increasingly popular. However, the tools in the majority of crystallization laboratories are focused on producing large single crystals by vapour diffusion that fit the cryo-cooled paradigm of modern synchrotron crystallography. This paper presents several case studies and some ideas and strategies on how to perform the conversion from a single crystal grown by vapour diffusion to the many thousands of micro-crystals required for modern serial crystallography grown by batch crystallization. These case studies aim to show (i) how vapour diffusion conditions can be converted into batch by optimizing the length of time crystals take to appear; (ii) how an understanding of the crystallization phase diagram can act as a guide when designing batch crystallization protocols; and (iii) an accessible methodology when attempting to scale batch conditions to larger volumes. These methods are needed to minimize the sample preparation gap between standard rotation crystallography and dedicated serial laboratories, ultimately making serial crystallography more accessible to all crystallographers.

20.
Elife ; 82019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31855181

RESUMO

Previously we reported that a process called inter-fork strand annealing (IFSA) causes genomic deletions during the termination of DNA replication when an active replication fork converges on a collapsed fork (Morrow et al., 2017). We also identified the FANCM-related DNA helicase Fml1 as a potential suppressor of IFSA. Here, we confirm that Fml1 does indeed suppress IFSA, and show that this function depends on its catalytic activity and ability to interact with Mhf1-Mhf2 via its C-terminal domain. Finally, a plausible mechanism of IFSA suppression is demonstrated by the finding that Fml1 can catalyse regressed fork restoration in vitro.


Assuntos
Proteínas Cromossômicas não Histona/genética , DNA Helicases/genética , Recombinação Genética , Proteínas de Schizosaccharomyces pombe/genética , Replicação do DNA/genética , Genoma Fúngico/genética , Mitose/genética , Schizosaccharomyces/genética
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