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    1. Cancer Biology

    Loss of p53 suppresses replication-stress-induced DNA breakage in G1/S checkpoint deficient cells

    Bente Benedict et al.
    During tumorigenesis loss of p53 not only abrogates cell cycle arrest and apoptosis, but also suppresses the induction of replication-stress-induced DNA double-stranded breaks.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint

    Nicolas Bigot et al.
    Two phosphorylation sites on 53BP1 are found to mediate interaction with TOPBP1-RAD9 and shown to be essential for assembling the G1 DNA damage checkpoint response apparatus.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

    Anna Caballe et al.
    ULK3 is a kinase in the abscission checkpoint that temporarily inactivates ESCRT-III proteins via phosphorylation, which is required to delay cytokinesis in response to defects in mitosis.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores

    Sushama Sivakumar et al.
    Microtubule binding by the Spindle and Kinetochore Associated (Ska) complex concentrates protein phosphatase 1 at metaphase kinetochores to overcome the spindle checkpoint thus driving anaphase onset and mitotic exit.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    ATR/Mec1 prevents lethal meiotic recombination initiation on partially replicated chromosomes in budding yeast

    Hannah G Blitzblau, Andreas Hochwagen
    During meiosis, budding yeast use a checkpoint involving the protein Mec1 to prevent the formation of double-strand breaks in DNA that has not completed replication.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

    Qiaozhen Ye et al.
    TRIP13 inactivates the spindle assembly checkpoint by converting MAD2 from its active ‘closed’ state to its inactive ‘open’ state.
    1. Chromosomes and Gene Expression

    The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress

    Takeshi Wakida et al.
    Minimizing anti-proliferation signaling from DNA damage detection machinery is the tactic for the cells to drive proliferation under genotoxic environment, and the function is exerted by Polo-Like-Kinase1 that is frequently over-expressed in cancer cells.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Proteolytic maturation of α2δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels

    Ivan Kadurin et al.
    Multiple roles of the auxiliary calcium channel α2δ subunits require proteolytic cleavage of the precursor protein into α2 and δ.
    1. Cancer Biology

    Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

    Christopher A Natale et al.
    Driving melanoma differentiation through G protein-coupled estrogen receptor signaling decreases proliferative capacity, decreases expression of the oncodriver and stem cell marker c-Myc, and increases the effectiveness of immunotherapy.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands

    Matthew Day et al.
    Structural and biochemical analyses of BRCT domain interactions defines TOPBP1/Rad4 selectivity for phosphorylated motifs, allowing identification of new interactions, and providing insights into assembly of different TOPBP1-scaffolded DNA repair complexes.