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     

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     

ATP alters the diffusion mechanics of MutS on mismatched DNA

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Highlights? The development and use of smFlow-FRET and smPolarization-TIRF microscopy ? Lesion-searching MutS rotationally diffuses in continuous contact with the DNA ? ATP-bound MutS spins freely and in discontinuous contact with the DNA backbone ? Direct visualization of multiple ATP-bound MutS clamps that diffuse along the DNA     

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     

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     

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     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome     

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     

Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA

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Highlights? Neil3 is an Fpg/Nei DNA glycosylase of the base excision repair pathway ? Neil3 excises a broad spectrum of base lesions, with a marked preference for ssDNA ? We report a crystal structure of Neil3 DNA glycosylase ? The structure provides valuable insights into Neil3′s unusual substrate specificity     

DNA Quality Control by a Lesion Sensor Pocket of the Xeroderma Pigmentosum Group D Helicase Subunit of TFIIH

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Highlights? Amino acid changes near the central pore of XPD confer defective excision repair ? These mutants retain DNA helicase activity when tested in an archaeal framework ? The mutants are unable to sense lesions during their ATP-driven tracking movement ? The mutants are unable to build a stable demarcation complex at DNA lesion sites     

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     

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     

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     

Structure of the Catalytic Region of DNA Ligase IV in Complex with an Artemis Fragment Sheds Light on Double-Strand Break Repair

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Highlights? The crystal structure of the DNA ligase IV/Artemis complex was solved at 2.4 Å ? The structure of DNA ligase IV (residues 1–609) shows inserts ? An Artemis helix forms a three-helix bundle with two helices from DNA ligase IV ? The structure provides insights into the mutations causing LIG4 syndrome     

A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation,CHK1 Activation,and DNA Repair

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Highlights? BRCA1 E3 ligase activity is essential for a subset of DNA damage responses ? BRCA1 V26A mutant cells are sensitive to topoisomerase inhibitors but not mitomycin C ? BRCA1 selectively ubiquitylates claspin after topoisomerase inhibition ? BRCA1 E3 ligase inactivation selectively impairs CHK1 activation     

Genomic Regions Flanking E-Box Binding Sites Influence DNA Binding Specificity of bHLH Transcription Factors through DNA Shape

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Highlights? Cbf1 and Tye7 are paralogous TFs with virtually identical DNA binding-site motifs ? The two paralogous TFs bind different genomic target sites in vivo ? The genomic context of putative DNA binding sites affects TF binding specificity ? Structural analyses suggest that genomic context influences TF binding through DNA shape     

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms

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Highlights? Constitutional complex chromosomal rearrangements display unanticipated complexity resembling chromothripsis ? Some chromothripsis rearrangements involve clustered double-stranded DNA breaks ? There exist distinct classes of chromothripsis rearrangements