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     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

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Highlights? We have determined the cryo-EM structures of ORC, ORC-DNA, and ORC-Cdc6-DNA ? We show that ORC is arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2 ? DNA and Cdc6 binding causes large conformational changes in ORC ? Origin DNA is proposed to bind to the interior surface of the crescent-shaped ORC     

Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells

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Highlights? PGCs differentiated from ESCs undergo genome-wide DNA demethylation ? Tet1 and Tet2 do not regulate genome-wide DNA demethylation in PGCs ? Tet1 and Tet2 regulate locus-specific demethylation in PGCs     

Short Telomeres in ESCs Lead to Unstable Differentiation

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Highlights? ESCs with short telomeres do not stably differentiate and can resume proliferation ? Critically short telomeres impair Nanog regulation during ESC differentiation ? Short telomeres elicit genome-wide DNA hypomethylation and altered H3K27me3 levels ? Impaired DNA methylation and differentiation are rescued by Dnmt3b or telomere elongation     

Human TFIID Binds to Core Promoter DNA in a Reorganized Structural State

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Highlights? TFIID has distinct conformations with different positions of the TBP-containing lobe ? A rearranged state of TFIID interacts with promoter DNA in a TFIIA-dependent manner ? TFIID induces multiple topological changes on promoter DNA around the start site ? The different conformations of TFIID may serve as targets for regulatory factors     

piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

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Highlights? MIWI is a substrate of APC/C, and piRNA loading is essential for MIWI ubiquitination ? piRNA loading promotes MIWI binding to the APC/C substrate-binding subunit ? MIWI and piRNAs are coordinately eliminated in late spermatids ? Inhibition of MIWI destruction in late spermatids prevents sperm maturation     

Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging

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Highlights? Locus-specific alterations of the DNA methylome accompany HSC aging ? Methylation changes target genes expressed downstream of HSCs to alter HSC potential ? HSC potential, DNA methylation, and replicative limits depend on divisional history ? Aging and forced proliferation of HSC results in DNA hypermethylation of PRC2 targets     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Sequence-Specific Transcription Factor NF-Y Displays Histone-like DNA Binding and H2B-like Ubiquitination

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Highlights? 3D structure of NF-Y/CCAAT shows close relationships to core histones H2A/H2B ? NF-YA displays a sequence-specific DNA minor groove-binding module ? Histone H2B and NF-YB share a functional posttranslational modification ? NF-Y binding and monoubiquitination are early events in gene activation     

Towards a structural understanding of PARP1 activation and related signalling ADP-ribosyl-transferases

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Highlights? PARP1 recognizes DNA strand breaks through substrate-assisted dimerization. ? PARP1 ZFIII and WGR domains link DNA break recognition to enzyme activation. ? Tankyrase-dependent PARylation regulates Wnt signalling and Cherubism syndrome.     

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     

Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation

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Highlights? Activation of the Brg1 chromatin-remodeling complex drives OPC differentiation ? Olig2 prepatterns and directs Brg1 targeting to oligodendrocyte-specific enhancers ? Functional and stage-dependent Olig2/Brg1 targeting in oligodendrocyte development ? Olig2/Brg1 targeting coupled with epigenetic marking defines oligodendrocyte identity     

Dissection of DNA Damage Responses Using Multiconditional Genetic Interaction Maps

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Highlights? A resource of genetic modules and networks induced by distinct types of DNA damage ? Networks distinguish DNA damage response pathways with high statistical power ? Rtt109, a histone acetyltransferase, affects the mutagenic bypass of DNA lesions ? The neddylation machinery and Irc21 affect cell-cycle control and genome stability     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Thrombopoietin-Increased DNA-PK-Dependent DNA Repair Limits Hematopoietic Stem and Progenitor Cell Mutagenesis in Response to DNA Damage

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Highlights? Mpl loss increases γ-irradiation-induced genomic instability in HSPCs ? TPO promotes DNA repair in vitro and in vivo in HSPCs ? TPO increases DNA-PK activity and NHEJ-mediated repair efficiency in HSPCs ? A single TPO injection before mouse TBI limits long-term HSC injury and mutagenesis