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     

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     

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     

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     

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     

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     

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     

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.     

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     

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     

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     

Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase

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Highlights? bAvd forms a highly positively charged pentameric barrel ? bAvd binds both DNA and RNA, but without sequence preference ? The coding sequence for bAvd serves dual purposes ? The interaction of bAvd with bRT is likely to be important for retrohoming     

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     

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     

Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

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Highlights? Fungicide-dependent reactive oxygen species production leads to fungal cellular death ? The TCA, ETC, and RAS/PKA pathways are involved in fungicide-induced cellular death ? Antifungals elevate mitochondrial activity, the AMP/ATP ratio, and sugar production ? DNA damage plays an important role in fungicide-induced cellular death     

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     

Efficient Retrograde Transport of Pseudorabies Virus within Neurons Requires Local Protein Synthesis in Axons

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Highlights? Pseudorabies virus (PRV) infection stimulates local protein synthesis in axons ? Infection induces the synthesis of LIS1, peripherin, and annexin A2 in axons ? Axonal inhibition of protein synthesis retards retrograde PRV capsid transport ? Prior damage in axons significantly reduces retrograde PRV capsid transport     

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     

Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages

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Highlights? M. tuberculosis permeabilizes phagosomes and activates cytosolic signaling pathways ? Host cytoplasmic DNA receptors sense M. tuberculosis extracellular DNA ? DNA recognition activates the STING/TBK1/IRF3 pathway ? Cytosolic sensing promotes M. tuberculosis infection