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作者：Keszthelyi, Andrea; Mansoubi, Sahar; Whale, Alex; Houseley, Jonathan; Baxter, Jonathan
作者单位：University of Sussex; Islamic Azad University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute
摘要：The fork protection complex (FPC), composed ofMrc1, Tof1, and Csm3, supports rapid and stable DNA replication. Here, we show that FPC activity also introduces DNA damage by increasing DNA topological stress during replication. Mrc1 action increases DNA topological stress during plasmid replication, while Mrc1 or Tof1 activity causes replication stress and DNA damage within topologically constrained regions. We show that the recruitment of Top1 to the fork by Tof1 suppresses the DNA damage gene...
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作者：Michalczyk, Elizabeth; Pakosz-Stepen, Zuzanna; Liston, Jonathon D.; Gittins, Olivia; Pabis, Marta; G. Heddle, Jonathan; Ghilarov, Dmitry
作者单位：Jagiellonian University; Jagiellonian University; Durham University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Center
摘要：Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization of a chiral DNA loop followed by the passage of the T- segment through the temporarily cleaved G- segment resulting in sign inversion. The molecular basis for this is poorly understood as the chiral loop has never been directly observed. We have obtained high- resolution cryoEM structures of Escherichia coli gyrase with chiral...
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作者：Jiao, Alan L.; Sendinc, Erdem; Zee, Barry M.; Wallner, Felice; Shi, Yang
作者单位：University of Oxford; Ludwig Institute for Cancer Research; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Cell Signaling Technology
摘要：The H3K27M oncogenic histone (oncohistone) mutation drives similar to 80% of incurable childhood brain tumors known as diffuse midline gliomas (DMGs). The major molecular feature of H3K27M mutant DMGs is a global loss of H3K27 trimethylation (H3K27me3), a phenotype conserved in Caenorhabditis elegans (C. elegans). Here, we perform unbiased genome-wide suppressor screens in C. elegans expressing H3K27M and isolate 20 suppressors, all of which at least partially restore H3K27me3. 19/20 suppresso...
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作者：Hicks, Jarrod M.; Mcdermott, Josh H.
作者单位：Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University
摘要：Human hearing is robust to noise, but the basis of this robustness is poorly understood. Several lines of evidence are consistent with the idea that the auditory system adapts to sound components that are stable over time, potentially achieving noise robustness by suppressing noise- like signals. Yet background noise often provides behaviorally relevant information about the environment and thus seems unlikely to be completely discarded by the auditory system. Motivated by this observation, we...
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作者：Kovalova, Terezia; Krol, Sylwia; Gamiz-Hernandez, Ana P.; Sjostrand, Dan; Kaila, Ville R. I.; Brzezinski, Peter; Hogbom, Martin
作者单位：Stockholm University
摘要：Tuberculosis is one of the most common causes of death worldwide, with a rapid emergence of multi- drug- resistant strains underscoring the need for new antituberculosis drugs. Recent studies indicate that lansoprazole-a known gastric proton pump inhibberculosis compounds. Yet, their inhibitory mechanism and site of action still remain unknown. Here, we combine biochemical, computational, and structural approaches to probe the interaction of LPZS with the respiratory chain supercomplex III2IV2...
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作者：Pasini, Damiano
作者单位：McGill University
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作者：Ravindran, Sandeep
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作者：Teixeira, Rodrigo Braz; Carugno, Giorgio; Neri, Izaak; Sartori, Pablo
作者单位：Universidade de Lisboa; University of London; King's College London
摘要：Biological mixtures, such as the cellular cytoplasm, are composed of a large number of different components. From this heterogeneity, ordered mesoscopic structures emerge, such as liquid phases with controlled composition. The competition of these structures for the same components raises several questions: what types of interactions allow the retrieval of multiple ordered mesoscopic structures, and what are the physical limitations for the retrieval of said structures. In this work, we develo...
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作者：Chang, Linda W.; Kirgios, Erika L.; Mullainathan, Sendhil; Milkman, Katherine L.
作者单位：University of Pennsylvania; University of Chicago; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
摘要：People often rely on numeric metrics to make decisions and form judgments. Numbers can be difficult to process, leading to their underutilization, but they also uniquely suited to making comparisons. Do people decide differently when dimensions of a choice are quantified and others are not? We explore this question across 21 preregistered experiments (8 in the main text, N = 9,303; 13 in supplement, N = 13,936) involving managerial, policy, and consumer decisions. Participants face choices tha...
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作者：Poles, Yonatan; Shi, Songlin; Fineberg, Jay
作者单位：Hebrew University of Jerusalem
摘要：Frictional slip between bodies having different elastic or geometrical properties (bimaterial interfaces) creates a unique type of rupture, bimaterial slip pulses. These slip pulses propagate along the interfaces separating elastically different contacting bodies. They exhibit highly localized slip with accompanying local normal stress reduction. These pulses do not result from properties of friction laws but, instead, are formed via the elastic mismatch of the contacting bodies. Here, we expe...
