The prereplication complex recruits XEco2 to chromatin to promote cohesin acetylation in Xenopus egg extracts

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Highlights? XEco2 loading and cohesin acetylation require pre-RC assembly but not DNA synthesis ? Two N-terminal motifs in XEco2 are essential for XEco2 loading and cohesion ? The PIP box in XEco2 contributes to cohesion ? Interaction of acetylated cohesin with DNA is stabilized after DNA replication     

Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer

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Highlights? C13 RNA aptamer variants stabilize GRK2 in a unique and remodeled conformation ? The aptamer positions an adenine nucleotide into the ATP-binding pocket of GRK2 ? Basic residues on an exterior surface of GRK2 facilitate aptamer binding ? The terminal stem of the aptamer indirectly contributes to affinity     

DNA Minor Groove Sensing and Widening by the CCAAT-Binding Complex

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Highlights? CBC binds to the minor groove of the DNA and bends it in a nucleosome-like manner ? Interactions of subunit HapB with DNA explain the sequence specificity of the CBC ? Anchor A of HapB tethers the CBC to the CCAAT box by minor groove widening ? Interactions of the CBC with the histones H3/H4 of the nucleosome are modeled     

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     

Development and Regeneration of Sox2+ Endoderm Progenitors Are Regulated by a HDAC1/2-Bmp4/Rb1 Regulatory Pathway

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Highlights? Hdac1/2 regulate development of Sox2+ endoderm progenitors ? Bmp4, Rb1, p21, and p16 are direct targets of Hdac1/2 in lung endoderm ? Increased Bmp4 suppresses Sox2 expression in lung endoderm ? Hdac1/2 are required for lung secretory epithelial regeneration     

Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

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Highlights? Cohesin is required for the association of its loader, Scc2/4, with centromeres ? The Ctf19 kinetochore subcomplex targets the loader to centromeres ? Centromere-loaded cohesin ensures pericentromeric cohesion establishment ? Cohesin ring formation triggers cohesin loading via Scc2/4     

Adaptation of Aminoacyl-tRNA Synthetase Catalytic Core to Carrier Protein Aminoacylation

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Highlights? The crystal structure of the aa:CP ligase in complex with carrier protein was solved ? The interaction relies on the idiosyncratic α-helix of the aa:CP ligase ? The complex represents a unique mode of carrier protein recognition and binding ? The mechanism of amino acid attachment to carrier protein is discussed     

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     

Crystal structures of a stabilized β1-adrenoceptor bound to the biased agonists bucindolol and carvedilol

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Highlights? Structures of β1AR bound to the biased agonists bucindololol and carvedilol ? The biased agonists form unique contacts with β1AR not seen with other antagonists ? The structures explain the pharmacological differences in the Arg389Gly polymorphism     

FANCM and FAAP24 Maintain Genome Stability via Cooperative as Well as Unique Functions

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Highlights? FANCM and FAAP24 exhibit nonepistatic functions in cell survival upon DNA damage ? FAAP24 confers unique lesion specificity in DNA damage cell-cycle checkpoint ? FANCM translocase activity is involved in recombination-independent ICL repair     

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3

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Highlights? The 3D structure of PKCι in complex with a peptide from Par-3 is determined ? PKCι does not need phosphorylation of Thr402 in its activation loop for its activity ? aPKCs do not need a priming kinase for their activations ? The PKCι/Par-3 structure reveals a unique substrate recognition patterns for aPKCs     

Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression

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Highlights? Rac1 and the Scar/WAVE complex drive pseudopod-based motility of melanoblasts ? Rac1-depleted melanoblasts move using unique actin-based stubs and not blebs ? Rac1 controls pseudopod frequency but is dispensable for pseudopod formation ? Loss of Rac1 delays melanoblast cell-cycle progression and cytokinesis     

A unique spatial arrangement of the snRNPs within the native spliceosome emerges from in silico studies

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Highlights? We present a computational procedure for fast matching of thousands of conformers ? We obtained a unique model localizing the snRNPs within the native spliceosome ? The 5 snRNPs are accommodated mostly within the large subunit of the spliceosome ? The large spliceosomal cavity emerges as the site of mRNA binding and splicing     

The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation

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Highlights? H2B ubiquitylation directly stimulates H3K4 methylation by the yeast Set1 complex ? Swd2 is not directly required for the H3K4 methylation activity of the yeast Set1 complex ? The Set1 n-SET domain plays a critical role in H2Bub-dependent H3K4 methylation ? Spp1 is conditionally involved in n-SET- and H2Bub-dependent H3K4 methylation     

Crystal structures of Aureochrome1 LOV suggest new design strategies for optogenetics

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Highlights? Crystal structures in dark and light states determined for Aureochrome1 LOV ? Significant light induced change observed in F298 and quaternary structure ? Potential photocycle mutant variants, altering the light-state lifetime, identified ? Possible mechanism of signaling in topologically unique Aureo1 speculated     

Replacement of Oct4 by Tet1 during iPSC Induction Reveals an Important Role of DNA Methylation and Hydroxymethylation in Reprogramming

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Highlights? Tet1 facilitates iPSC induction by promoting Oct4 demethylation and reactivation ? Tet1 can replace Oct4 to generate fully pluripotent TSKM iPSCs ? Both 5mC and 5hmC increase on the genome during TSKM 2° reprogramming ? 5hmC promotes the demethylation of pluripotency genes during reprogramming     

Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4

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Highlights? SCF ubiquitin ligase subunit Fbx4 binds TRF1 using an atypical small GTPase fold ? Fbx4 recognizes a globular domain of TRF1, not just short phosphorylated degrons ? Telomere shelterin component TIN2 competes with Fbx4 for TRF1 binding ? TIN2 and SCF^Fbx4 thus control TRF1 ubiquitination and degradation     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis