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    1. Evolutionary Biology
    2. Structural Biology and Molecular Biophysics

    Structurally distributed surface sites tune allosteric regulation

    James W McCormick et al.
    Deep mutational scanning of a synthetic allosteric chimera revealed that a sparse set of mutations on the protein surface improved regulation.
    1. Biochemistry and Chemical Biology

    Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

    Fanny Sunden et al.
    Conventional studies have focused on enzymatic residues directly involved in catalysis; dissecting a potential interaction network within which these ‘catalytic residues’ are embedded provides insights fundamental to enzyme function, evolution, and engineering.
    1. Cancer Biology

    Overcoming mutation-based resistance to antiandrogens with rational drug design

    Minna D Balbas et al.
    Mutagenesis studies identified an androgen receptor mutation that converts enzalutamide-a drug recently approved for the treatment of advanced prostate cancer-into an androgen receptor agonist, and modeling studies informed the design of novel drugs that are effective against the mutant receptor.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides

    Samuel T Coradetti et al.
    Using barcoded mutagenesis and a high-throughput genetic screen results in the identification of 150 genes that affect lipid accumulation in a non-model yeast system.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Structural determinants of voltage-gating properties in calcium channels

    Monica L Fernández-Quintero et al.
    Structure modeling, site-directed mutagenesis, and current recordings revealed the mechanism by which stabilization of voltage sensors in the resting and activated states determines the gating properties of the CaV1.1 calcium channel.
    1. Cell Biology

    Optimized Vivid-derived Magnets photodimerizers for subcellular optogenetics in mammalian cells

    Lorena Benedetti et al.
    eMags is an engineered photodimerizer pair for optogenetic modulation in mammalian cells that is especially suited for the manipulation of intracellular processes occurring in small volumes or subcellular organelles.
    1. Microbiology and Infectious Disease

    The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis

    Anat Melamed et al.
    The human leukemia virus HTLV-1 causes abnormal chromatin looping in tens of thousands of infected T cell clones in each host, and abnormal host transcription both flanking the integrated provirus and at distant loci in cis.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

    Karl P Hodel et al.
    When mismatch repair is compromised heterozygous loss of Pol ε proofreading is sufficient to drive a subset of the observed clinical characteristics of Pol ε tumors.
    1. Cancer Biology

    CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials

    Ann Lin et al.
    A putative therapeutic target undergoing clinical trials in breast cancer is non-essential and the drug used in those trials blocks cell division through an off-target effect.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells

    Erik C Hansen et al.
    Uracil/adenine base pairs in HIV-1 DNA are attacked by the uracil base excision repair machinery in macrophages, which leads to HIV restriction and viral genome diversification by transcription-associated mutagenesis.