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Tumor-suppressor protein CYLD cleaves linear and Lys63-linked ubiquitin chains. Structures of CYLD USP domain with Met1- and Lys63-linked diubiquitins and biochemical analyses reveal the mechanism for dual specificity and provide insight into tumor-associated mutations.
The identification of a new subclass of circular RNAs that are predominantly nuclear and promote transcription of their parental genes reveals a new regulatory function for these noncoding RNAs.
Genome-wide DNA polymerase usage maps determined in fission yeast, using a new sequencing strategy based on ribonucleotide misincorporation, track the division of labor between replicative polymerases and reveal locations and efficiencies of replication origins.
The crystal structure of Yersinia enterocolitica kinase YopO in complex with monomeric actin, together with biochemical analyses, reveals that YopO uses actin as bait to disrupt host cytoskeleton function and prevent phagocytosis.
Human DNA Polθ can mediate microhomology-mediated end-joining (MMEJ) of DNA molecules in cells and in vitro. Biochemistry work shows that Polθ promotes formation of DNA synapses and strand annealing, activities that require insertion loop 2.
The neuronal sorting receptor SorLA protects against Alzheimer's disease by binding Aβ peptides. Three new structures of the Vps10p Aβ-binding domain in ligand-free and ligand-bound forms explain the basis of SorLA peptide recognition.
New biochemical analyses in Xenopus cell-free extracts show that two replication forks must converge on a DNA interstrand cross-link (ICL) to permit translesion synthesis and repair.
The proteasome initiates protein degradation at disordered regions within substrates. The proteasomal sequence preferences for the amino acid composition of these regions identified here affect protein half-life and explain unusual stability trends.
Oxidative stress induces a number of cellular responses. Silva et al. uncover a peroxide-mediated K63-linked polyubiquitination pathway, and identify its targets and regulators.
HydEn-seq, a new sequencing method that maps the distribution of ribonucleotides misincorporated by low-fidelity DNA polymerases in budding yeast, reveals unexpected strand-specific replication patterns in both nuclear and mitochondrial genomes.
Toll-like receptors (TLRs) have key roles in innate immunity. Here, Shimizu and colleagues report crystal structures of TLR8 in complex with single-stranded RNA that reveal the molecular basis for recognition of a natural ligand.
Aquarius is an RNA helicase associated with spliceosomes. Lührmann, Pena and colleagues now provide structural insights into how Aquarius is recruited to the spliceosome, revealing a new spliceosomal building block that aids in Aquarius positioning.
The γ-tubulin ring complex (γTuRC) nucleates microtubules in the cell. The functional, closed state of yeast γTuRC is now visualized, and its microtubule-nucleating activity is found to be species specific.
Structural, computation and kinetics approaches reveal the energy landscape of catalysis by adenylate kinase and show that the cofactor Mg2+ activates two distinct molecular events in the reaction cycle: phosphoryl transfer and lid opening.
Structural, biophysical and genetic analyses reveal that Schizosaccharomyces pombe Ctp1 forms a flexible tetramer with multivalent DNA-binding and bridging activities that contribute to Ctp1's role in repair of DNA double-strand breaks.
Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.
Proteins with charged amino acid residues encounter an electric force as they transit through membranes holding membrane potential. Von Heijne and colleagues measure this force to assess how membrane electrostatics contributes to translocation dynamics.
CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination.