Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends

Mammalian cells require Nonhomologous end joining (NHEJ) for efficient repair of chromosomal DNA double-strand breaks1. A key feature of biological sources of strand breaks is associated nucleotide damage, including base loss (abasic or AP sites)2. At single strand breaks, 5' terminal abasic sites are excised by pol β's 5'dRP lyase activity3,4,5,6: we show here in vitro and in cells that accurate and efficient repair by NHEJ of double-strand breaks with such damage similarly requires 5'dRP/AP lyase activity (Figure 1a). Classically defined NHEJ is moreover uniquely effective at coupling this end-cleaning step to joining in cells, helping distinguish this pathway from otherwise robust alternate NHEJ pathways. Surprisingly, the NHEJ factor Ku can be identified as an effective 5'dRP/AP lyase. Similar to other lyases7, Ku nicks DNA 3' of an abasic site by a mechanism involving a Schiff base covalent intermediate with the abasic site. We demonstrate using cell extracts that Ku is essential for efficient removal of AP sites near double-strand breaks and, consistent with this result, joining of such breaks is specifically reduced in cells complemented with a lyase-attenuated Ku mutant. Ku had previously been presumed only to recognize ends and recruit other factors that processed ends; our data supports an unexpected direct role for Ku in end processing steps as well

Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purkinje neurons and synaptic disorganization in the deep cerebellar nucleus (DCN). The sacsin interactome reveals that sacsin regulates interactions between cytoskeletal and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Long- and short-range correlations and their event-scale dependence in high-multiplicity pp collisions at 1as = 13 TeV

Two-particle angular correlations are measured in high-multiplicity proton-proton collisions at s = 13 TeV by the ALICE Collaboration. The yields of particle pairs at short-( 06\u3b7 3c 0) and long-range (1.6 < | 06\u3b7| < 1.8) in pseudorapidity are extracted on the near-side ( 06\u3c6 3c 0). They are reported as a function of transverse momentum (pT) in the range 1 < pT< 4 GeV/c. Furthermore, the event-scale dependence is studied for the first time by requiring the presence of high-pT leading particles or jets for varying pT thresholds. The results demonstrate that the long-range \u201cridge\u201d yield, possibly related to the collective behavior of the system, is present in events with high-pT processes as well. The magnitudes of the short- and long-range yields are found to grow with the event scale. The results are compared to EPOS LHC and PYTHIA 8 calculations, with and without string-shoving interactions. It is found that while both models describe the qualitative trends in the data, calculations from EPOS LHC show a better quantitative agreement for the pT dependency, while overestimating the event-scale dependency. [Figure not available: see fulltext.

f0(980) production in inelastic pp collisions at s = 5.02 TeV

The measurement of the production of f0(980) in inelastic pp collisions at sqrt(s) = 5.02 TeV is presented. This is the first reported measurement of inclusive f0(980) yield at LHC energies. The production is measured at midrapidity, |y| pi+pi- hadronic decay channel using the ALICE detector. The pT-differential yields are compared to those of pions, protons and ϕ mesons as well as to predictions from the HERWIG 7.2 QCD-inspired Monte Carlo event generator and calculations from a coalescence model that uses the AMPT model as an input. The ratio of the pT-integrated yield of f0(980) relative to pions is compared to measurements in e+e- and pp collisions at lower energies and predictions from statistical hadronisation models and HERWIG 7.2. A mild collision energy dependence of the f0(980) to pion production is observed in pp collisions from SPS to LHC energies. All considered models underpredict the pT-integrated 2f0(980)/(pi+ + pi-) ratio. The prediction from the canonical statistical hadronisation model assuming a zero total strangeness content of f0(980) is consistent with the data within 1.9σ and is the closest to the data. The results provide an essential reference for future measurements of the particle yield and nuclear modification in p–Pb and Pb–Pb collisions, which have been proposed to be instrumental to probe the elusive nature and quark composition of the f0(980) scalar meson

Pion-kaon femtoscopy and the lifetime of the hadronic phase in Pb-Pb collisions at root(S)(NN)=2.76 TeV

In this paper, the first femtoscopic analysis of pion-kaon correlations at the LHC is reported. The analysis was performed on the Pb-Pb collision data at root(S)(NN) = 2.76 TeV recorded with the ALICE detector. The non-identical particle correlations probe the spatio-temporal separation between sources of different particle species as well as the average source size of the emitting system. The sizes of the pion and kaon sources increase with centrality, and pions are emitted closer to the centre of the system and/or later than kaons. This is naturally expected in a system with strong radial flow and is qualitatively reproduced by hydrodynamic models. ALICE data on pion-kaon emission asymmetry are consistent with (3+1)-dimensional viscous hydrodynamics coupled to a statistical hadronisation model, resonance propagation, and decay code THERMINATOR 2 calculation, with an additional time delay between 1 and 2 fm/c for kaons. The delay can be interpreted as evidence for a significant hadronic rescattering phase in heavy-ion collisions at the LHC. (C) 2020 The Author. Published by Elsevier B.V.Peer reviewe

Elliptic and triangular flow of (anti)deuterons in Pb-Pb collisions at sNN =5.02 TeV

The measurements of the (anti)deuteron elliptic flow (v2) and the first measurements of triangular flow (v3) in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision √sNN = 5.02 TeV are presented. A mass ordering at low transverse momentum (pT) is observed when comparing these measurements with those of other identified hadrons, as expected from relativistic hydrodynamics. The measured (anti)deuteron v2 lies between the predictions from the simple coalescence and blast-wave models, which provide a good description of the data only for more peripheral and for more central collisions, respectively. The mass number scaling, which is violated for v2, is approximately valid for the (anti)deuterons v3. The measured v2 and v3 are also compared with the predictions from a coalescence approach with phase-space distributions of nucleons generated by IEBEVISHNU with AMPT initial conditions coupled with URQMD, and from a dynamical model based on relativistic hydrodynamics coupled to the hadronic afterburner SMASH. The model predictions are consistent with the data within the uncertainties in midcentral collisions, while a deviation is observed in the most central collisions