299 research outputs found

    The S phase checkpoint promotes the Smc5/6 complex dependent SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε

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    Replication fork stalling and accumulation of single-stranded DNA trigger the S phase checkpoint, a signalling cascade that, in budding yeast, leads to the activation of the Rad53 kinase. Rad53 is essential in maintaining cell viability, but its targets of regulation are still partially unknown. Here we show that Rad53 drives the hyper-SUMOylation of Pol2, the catalytic subunit of DNA polymerase ε, principally following replication forks stalling induced by nucleotide depletion. Pol2 is the main target of SUMOylation within the replisome and its modification requires the SUMO-ligase Mms21, a subunit of the Smc5/6 complex. Moreover, the Smc5/6 complex co-purifies with Pol ε, independently of other replisome components. Finally, we map Pol2 SUMOylation to a single site within the N-terminal catalytic domain and identify a SUMO-interacting motif at the C-terminus of Pol2. These data suggest that the S phase checkpoint regulate Pol ε during replication stress through Pol2 SUMOylation and SUMO-binding abilit

    A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles

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    Eukaryotic cells use a multi-layered immune response to combat intracellular pathogens. The ubiquitin ligase ZNFX1 has emerged as a crucial yet little understood player that regulates the immune response while protecting against RNA viruses. Our study unveils the molecular mechanism of ZNFX1, mediated by the joint activity of a helicase serving as a nucleic acid sensor and a non-conventional E3 module featuring a split active site. We demonstrate that single-stranded RNA stimulates E3 activity by fostering dimerization of ZNFX1 subunits that translocate along nucleic acid tracks. Juxtaposed E3 domains complement each other, leading to the ubiquitination of ZNFX1 itself and engaged RNA molecules, while clustering nucleic acids into dense nucleoprotein particles. We show that the E3 ligase activity of ZNFX1 protects cells during an immune response and propose that ubiquitin-coated particles formed by ZNFX1 represent part of an ancient mechanism to regulate both foreign and host RNA in the cell

    Measurements of the production cross-sections of a Higgs boson in association with a vector boson and decaying into WW * with the ATLAS detector at s = 13 TeV

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    Measurements of the total and differential Higgs boson production cross-sections, via WH and ZH associated production using H → WW* → ℓνℓν and H → WW* → ℓνjj decays, are presented. The analysis uses proton-proton events delivered by the Large Hadron Collider at a centre-of-mass energy of 13 TeV and recorded by the ATLAS detector between 2015 and 2018. The data correspond to an integrated luminosity of 140 fb−1. The sum of the WH and ZH cross-sections times the H → WW* branching fraction is measured to be 0.44−0.09+0.10stat.−0.05+0.06syst. pb, in agreement with the Standard Model prediction. Higgs boson production is further characterised through measurements of the differential cross-section as a function of the transverse momentum of the vector boson and in the framework of Simplified Template Cross-Sections

    Search for supersymmetry using vector boson fusion signatures and missing transverse momentum in pp collisions at s = 13 TeV with the ATLAS detector

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    This paper presents a search for supersymmetric particles in models with highly compressed mass spectra, in events consistent with being produced through vector boson fusion. The search uses 140 fb−1 of proton-proton collision data at s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Events containing at least two jets with a large gap in pseudorapidity, large missing transverse momentum, and no reconstructed leptons are selected. A boosted decision tree is used to separate events consistent with the production of supersymmetric particles from those due to Standard Model backgrounds. The data are found to be consistent with Standard Model predictions. The results are interpreted using simplified models of R-parity-conserving supersymmetry in which the lightest supersymmetric partner is a bino-like neutralino with a mass similar to that of the lightest chargino and second-to-lightest neutralino, both of which are wino-like. Lower limits at 95% confidence level on the masses of next-to-lightest supersymmetric partners in this simplified model are established between 117 and 120 GeV when the lightest supersymmetric partners are within 1 GeV in mass

    Search for long-lived charged particles using large specific ionisation loss and time of flight in 140 fb − 1 of pp collisions at s = 13 TeV with the ATLAS detector

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    This paper presents a search for massive, charged, long-lived particles with the ATLAS detector at the Large Hadron Collider using an integrated luminosity of 140 fb−1 of proton-proton collisions at s = 13 TeV. These particles are expected to move significantly slower than the speed of light. In this paper, two signal regions provide complementary sensitivity. In one region, events are selected with at least one charged-particle track with high transverse momentum, large specific ionisation measured in the pixel detector, and time of flight to the hadronic calorimeter inconsistent with the speed of light. In the other region, events are selected with at least two tracks of opposite charge which both have a high transverse momentum and an anomalously large specific ionisation. The search is sensitive to particles with lifetimes greater than about 3 ns with masses ranging from 200 GeV to 3 TeV. The results are interpreted to set constraints on the supersymmetric pair production of long-lived R-hadrons, charginos and staus, with mass limits extending beyond those from previous searches in broad ranges of lifetime

    Probing the Higgs boson CP properties in vector-boson fusion production in the H → τ + τ − channel with the ATLAS detector

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    The CP properties of the Higgs boson are studied in the vector-boson fusion production mode. The analysis exploits the decay mode of the Higgs boson into two τ-leptons using 140 fb−1 of proton-proton collision data at s=13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Results are obtained using the Optimal Observable method. CP-violating interactions between the Higgs boson and electroweak gauge bosons are considered in the effective field theory framework, with the interaction strength described in the HISZ basis by d~, and in the Warsaw basis by cHW~, cHB~, and cHW~B. No deviations relative to the Standard Model are observed, and limits are obtained on the strength parameters. The d~ parameter is constrained to the interval [−0.012, 0.044] at the 95% confidence level while cHW~ is constrained to [−0.24, 0.83], when considering both linear and quadratic effects of physics beyond the Standard Model

    Search for vector-like leptons coupling to first- and second-generation Standard Model leptons in pp collisions at s = 13 TeV with the ATLAS detector

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    A search for pair production of vector-like leptons coupling to first- and second-generation Standard Model leptons is presented. The search is based on a dataset of proton-proton collisions at s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1. Events are categorised depending on the flavour and multiplicity of leptons (electrons or muons), as well as on the scores of a deep neural network targeting particular signal topologies according to the decay modes of the vector-like leptons. In each of the signal regions, the scalar sum of the transverse momentum of the leptons and the missing transverse momentum is analysed. The main background processes are estimated using dedicated control regions in a simultaneous fit with the signal regions to data. No significant excess above the Standard Model background expectation is observed and limits are set at 95% confidence level on the production cross-sections of vector-like electrons and muons as a function of the vector-like lepton mass, separately for SU(2) doublet and singlet scenarios. The resulting mass lower limits are 1220 GeV (1270 GeV) and 320 GeV (400 GeV) for vector-like electrons (muons) in the doublet and singlet scenarios, respectively

    Search for same-charge top-quark pair production in pp collisions at s = 13 TeV with the ATLAS detector

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    A search for the production of top-quark pairs with the same electric charge (tt or tt¯) is presented. The analysis uses proton-proton collision data at s = 13 TeV, recorded by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1. Events with two same-charge leptons and at least two b-tagged jets are selected. Neural networks are employed to define two selections sensitive to additional couplings beyond the Standard Model that would enhance the production rate of same-sign top-quark pairs. No significant signal is observed, leading to an upper limit on the total production cross-section of same-sign top-quark pairs of 1.6 fb at 95% confidence level. Corresponding limits on the three Wilson coefficients associated with the Otu1, OQu1, and OQu8 operators in the Standard Model Effective Field Theory framework are derived

    Cross-section measurements for the production of a W -boson in association with high-transverse-momentum jets in pp collisions at s = 13 TeV with the ATLAS detector

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    A set of measurements for the production of a W-boson in association with high-transverse-momentum jets is presented using 140 fb-1 of proton–proton collision data at a centre-of-mass energy of s=13 TeV collected by the ATLAS detector at the LHC. The measurements are performed in final states in which the W-boson decays into an electron or muon plus a neutrino and is produced in association with jets with pTEMPTY>30 GeV, where the leading jet has pTEMPTY>500 GeV. The angular separation between the lepton and the closest jet with pTEMPTY>100 GeV is measured and used to define a collinear phase space, wherein measurements of kinematic properties of the W-boson and the associated jet are performed. The collinear phase space is populated by dijet events radiating a W-boson and events with a W-boson produced in association with several jets and it serves as an excellent data sample to probe higher-order theoretical predictions. Measured differential distributions are compared with predictions from state-of-the-art next-to-leading order multi-leg merged Monte Carlo event generators and a fixed-order calculation of the W+1-jet process computed at next-to-next-to-leading order in the strong coupling constant
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