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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.
Cellular fate is determined by transcriptional networks and epigenetic states. In addition to protein factors, noncoding RNAs (ncRNAs), particularly microRNAs and long ncRNAs, are able to remodel transcriptional circuits and reshape epigenetic landscapes. This Commentary highlights the emerging roles of these ncRNAs in cellular reprogramming, transdifferentiation and organ regeneration.
The long-held view that the primary role of RNA is to code for proteins has been severely undermined. This Focus explores the remarkable functional diversity of RNA in light of recent breakthroughs in noncoding-RNA biology.
Recent advances in RNA-sequencing technologies have led to the discovery of thousands of previously unannotated noncoding transcripts, including many long noncoding RNAs (lncRNAs) whose functions remain largely unknown. Here, the authors discuss considerations and best practices when identifying and annotating lncRNAs that should aid their functional and mechanistic exploration.
The natural versatility of RNA makes it an ideal substrate for bioengineering. Its structural properties and predictable base-pairing permit its use as molecular scaffold, and its ability to interact with nucleic acids, proteins and small molecules confers a regulatory potential that can be harvested to design RNA regulators in diverse contexts.
The ribosome is a complex molecular machine that is central to protein synthesis. This Review highlights the various roles of noncoding RNAs during the different steps of ribosome biogenesis and discusses the consequences for ribosome function.
