A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice

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Highlights? 53BP1 inhibits BRCA1 recruitment to DSB sites in G1 ? RIF1 is the effector of 53BP1 during DSB repair ? Class-switch recombination requires RIF1 ? RIF1 recruitment to DSB sites in S/G2 is inhibited by BRCA1-CtIP     

Homologous Recombination DNA Repair Genes Play a Critical Role in Reprogramming to a Pluripotent State

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Highlights? Reprogramming increases the level of γH2AX, a marker of DNA DSBs ? Homologous recombination (HR) deficiency impairs reprogramming ? Reprogramming-induced DSBs and HR phenotypes are method-independent ? p53 deletion rescues reprogramming defects in HR-deficient cells     

HMGB1-Facilitated p53 DNA Binding Occurs via HMG-Box/p53 Transactivation Domain Interaction,Regulated by the Acidic Tail

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Highlights? Binding of p53 to its cognate DNA is facilitated by HMGB1 ? The N-terminal region of p53 (residues 38–61; TAD2) interacts with the HMG boxes ? The acidic tail of HMGB1 masks the p53 binding site in the free proteins ? The structure of the A-box/p53(1–93) complex shows that TAD2 acts as an ss-DNA mimic     

Protein Determinants of Meiotic DNA Break Hot Spots

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Highlights? DSB hot spots for meiotic recombination are specified by largely unknown mechanisms ? Linear element proteins, required for most DSBs, are highly enriched at hot spots ? These proteins, the first known global hot spot determinants, bind without DSB formation ? Hot spot determination by these proteins provides a paradigm for crossover control     

Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations

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Highlights? Complex chromosomal alterations (chromothripsis) observed in medulloblastomas ? Cancers with such alterations harbor TP53 mutations ? Context-specific link between the status of p53 and likelihood of chromothripsis ? p53 status and chromothripsis also correlate with aggressive acute myeloid leukemia     

Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation

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Highlights? Cocrystal structure of KRIT1 with ICAP1 shows a bidentate interaction interface ? Cocrystal structure of ICAP1 with integrin β1 shows a PTB-peptide interaction ? KRIT1 antagonizes ICAP1-modulated integrin activation by the bidentate interaction ? KRIT1 contains a previously undescribed N-terminal Nudix domain     

The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme

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Highlights? The first structure of a nuclear PP1 holoenzyme, NIPP1:PP1 ? The NIPP1 helix defines a unique interaction site on PP1 ? Identification of a common PP1-binding pocket, the ΦΦ motif-binding pocket ? Explains the mechanism of nuclear substrate selection by PP1     

POT1-TPP1 Regulates Telomeric Overhang Structural Dynamics

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Highlights? POT1 binds the telomere overhang sequentially one OB fold at a time ? POT1 binding exhibits 3′ to 5′ directionality ? POT1-TPP1N induces dynamic folding and unfolding of telomeric overhang ? POT1-TPP1N slides back and forth on the telomeric overhang     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

An OsCEBiP/OsCERK1-OsRacGEF1-OsRac1 Module Is an Essential Early Component of Chitin-Induced Rice Immunity

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Highlights? Chitin induces rapid activation of the rice small GTPase OsRac1 at the plasma membrane ? OsRacGEF1 interacts with and acts as a guanine nucleotide exchange factor for OsRac1 ? In response to chitin, OsRacGEF1 is activated via phosphorylation by OsCERK1 ? OsRacGEF1 is required for chitin-driven immunity and resistance to rice blast fungus     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

Metabolic Stress Controls mTORC1 Lysosomal Localization and Dimerization by Regulating the TTT-RUVBL1/2 Complex

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Highlights? Glucose and glutamine feed back to promote mTORC1 signaling through ATP production ? Energetic stress prevents mTOR lysosomal localization independently of AMPK and Rag ? ATP-dependent TTT-RUVBL complex is disassembled and repressed by energetic stress ? TTT-RUVBL is required for mTORC1 functional assembly and lysosomal localization     

Structural and functional analysis of HtrA1 and its subdomains

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Highlights? IGFBP-like domain structure suggests that it is incompetent for IGF binding ? Kazal-like domain structure shows distorted “P1” loop incompetent for inhibition ? Protease domain shows catalytic readiness in apo form ? SAXS envelope for full-length HtrA1     

The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1

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Highlights? Ensconsin is required for cargo transport driven by kinesin-1 ? The C terminus of ensconsin activates kinesin-1; its N terminus binds microtubules ? Kinesin-1 mutants without autoinhibitory activity do not require ensconsin     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Conversion of a Signal into Forces for Axon Outgrowth through Pak1-Mediated Shootin1 Phosphorylation

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Highlights? An attractive guidance cue, netrin-1, induces Pak1-mediated shootin1 phosphorylation ? Pak1-mediated shootin1 phosphorylation enhances clutch engagement at growth cones ? Pak1-mediated shootin1 phosphorylation promotes formation of traction forces ? Pak1-mediated shootin1 phosphorylation promotes axon outgrowth