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Volume 13 Issue 1, January 2017

The cover depicts an acidic patch of ubiquitin (purple) on a chromatin fiber (gray structure) displayed on a background showing cross-peaks from hydrogen-deuterium exchange nuclear magnetic resonance analysis. The image is based on PDB 1UBQ and EMD 2600 visualized with the program Chimera. Cover design by Erin Dewalt, based on an image created by Galia Debelouchina. Article, p105

Research Highlights

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News & Views

  • New approaches allow tight control over Cas9 activity using chemical induction. These studies expand the ability to rapidly induce and suppress Cas9-mediated nuclease activity and conditionally modulate the multiplex regulation of endogenous gene expression.

    • Isaac B Hilton
    • Charles A Gersbach
    News & Views
  • Ferroptosis is characterized by accumulation of lipid peroxidation products and lethal ROS, but the source and identity of lipid death signals that cause toxicity are poorly defined. New studies reveal that ACSL4 controls sensitivity to ferroptosis and that oxidized phosphatidylethanolamines are critical for ferroptosis execution.

    • Katharina D'Herde
    • Dmitri V Krysko
    News & Views
  • The Global Natural Products Social Molecular Networking (GNPS) resource and the DEREPLICATOR algorithm provide new tools for analyzing mass spectral data and enabling natural products discovery.

    • Mark E Horsman
    • Christopher N Boddy
    News & Views
  • The role of RAS dimerization in tumor biology is an emerging area of preclinical cancer research. Characterization of a RAS monobody indicates that dimer formation is required for RAS signaling, revealing the dimer interface as a potential drug target.

    • Matthew Holderfield
    • Deborah K Morrison
    News & Views
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Brief Communication

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  • Structural and biochemical studies of the histone acetyltransferase p300 in complex with acyl-CoA substrates reveal a lysine binding channel that accommodates a particular chain length to mediate efficient histone modification.

    • Zuzanna Kaczmarska
    • Esther Ortega
    • Daniel Panne
  • Aggregated mass spectral data by consortia such as the Global Natural Products Social (GNPS) molecular networking infrastructure enable natural product discovery. DEREPLICATOR, validated on peptidic natural products, is a computational tool to identify known metabolites in complex samples.

    • Hosein Mohimani
    • Alexey Gurevich
    • Pavel A Pevzner
  • A systems-level look at the activation of joint synovial fibroblasts in rheumatoid arthritis patients in response to different activators and therapeutic kinase inhibitors shows that multivariate inhibitor effects depend on the nature of the activator, not on the disease state per se.

    • Douglas S Jones
    • Anne P Jenney
    • Peter K Sorger
  • Carbapenem β-lactam antibiotics target non-classical transpeptidases, the L,D-transpeptidases, which act in an alternative Mycobacterium tuberculosis peptidoglycan synthesis pathway, informing the design of evolved carbapenems with improved antibacterial activity.

    • Pankaj Kumar
    • Amit Kaushik
    • Gyanu Lamichhane
  • Arachidonyl and adrenoyl PE phospholipids generated by ACSL4, an acyl-CoA synthase, are doubly or triply oxidized by lipoxygenases and other iron-containing sources of oxidation to promote ferroptotic cell death.

    • Valerian E Kagan
    • Gaowei Mao
    • Hülya Bayır
  • Single-molecule high-resolution optical trapping techniques elucidate the molecular mechanisms underlying the unwinding of RNA duplexes by the helicase Mtr4p, including how it restricts directional translocation to duplex regions.

    • Eric M Patrick
    • Sukanya Srinivasan
    • Matthew J Comstock
  • Hydrogen–deuterium (H/D) exchange combined with NMR spectroscopy analysis of nucleosomal arrays identified an acidic patch on ubiquitin that mediates chromatin decompaction and further supports that ubiquitin–ubiquitin interactions are needed for chromatin solubilization.

    • Galia T Debelouchina
    • Karola Gerecht
    • Tom W Muir
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