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Accumulation of extrachromosomal telomere repeats in the cytoplasm activates the cGAS-STING pathway, and this mechanism is suppressed in ALT cancer cells. Image by Aleksandr Ugorenkov / Alamy Stock Photo. (p 1124)
The helicase intrinsic to DNA polymerase θ (Polθ), the versatile mediator of microhomology-based repair of DNA double-strand breaks and stalled replication forks, is now revealed to be a member of an elite group of proteins known as annealing helicases. This small family of enzymes remodels DNA intermediates in multiple repair processes that are crucial to preserving genome stability and warding off cancer and aging.
The crystal structure of an oligosaccharyltransferase in complex with a sugar donor and an acceptor peptide provides insight into the mechanism of protein glycosylation and reveals how lipid-linked oligosaccharides are positioned in the enzyme active site.
Deadenylation of mRNAs is generally associated with translational inhibition and mRNA decay. A study now reports that, unexpectedly, highly expressed genes tend to have shorter poly(A) tails and suggests that poly(A) tails can be 'pruned', generating a 30-nucleotide-biased phased distribution, likely due to protection by poly(A)-binding proteins.
In this Review, the authors consider how single-molecule biophysical approaches can inform our understanding of the ring-shaped structural maintenance of chromosome (SMC) complexes and their function in chromosome organization.
The mechanics and mechanisms of ribosomal translocation, including the conformational rearrangements in the ribosome and the roles of EF-G and tRNAs, are discussed in this Perspective by Mohan, Noller and colleagues.
Biochemical reconstitution of PRC2 interactions with chromatinized templates demonstrates that protein-free linker DNA dominates the PRC2-nucleosome interaction, while RNA inhibits binding.
Histone H3 lysine 14 is propionylated and butyrylated in vivo in a metabolic-state-dependent manner and these modifications promote high levels of transcription.
Although deadenylation induces translational inhibition and mRNA decay, well-expressed transcripts are now shown to possess short, well-defined poly(A) tails, suggesting that pruned tails may be ideal for protective and translational functions.
Structural and functional analyses of human TRF1 in complex with meiosis-specific protein TERB1 reveal the basis for telomere tethering to the inner nuclear membrane and offer insight into the mechanism of dissociation in late pachytene.
Disrupting the interaction between telomere protein TRF1 with meiosis-specific protein TERB1 impairs the pairing of X and Y chromosomes via their telomere-adjacent pseudoautosomal regions in pachytene, leading to spermatocyte apoptosis and male infertility in mice.
CD28 signaling motifs are sequestered within the membrane via interactions with phospholipids. TCR activation increases the local Ca2+ concentration, which disrupts CD28-lipid interactions.
Apolipoprotein A-I (apoA-I) is the scaffold protein that is essential for the assembly and function of HDL particles. A structural model for monomeric, lipid-free apoA-I, based on previous and new data, is now presented.
The crystal structure of the single-subunit oligosaccharyltransferase PglB in complex with acceptor peptide and a synthetic lipid-linked oligosaccharide analog reveals a key intermediate in the reaction mechanism.
Abnormal pre-60S particles are able to escape nuclear quality control and join mature 40S subunits to catalyze cytoplasmic protein synthesis, but the resulting translation defects trigger the cytoplasmic surveillance machineries RQC and the Ski-exosome.
Biochemical and cellular analyses reveal that the helicase activity of DNA polymerase theta (Polθ) antagonizes RPA to promote DNA strand annealing and double-strand break repair via alt-NHEJ in mouse ES cells.
The cGAS-STING cytoplasmic-DNA-sensing pathway is activated by accumulation of extrachromosomal telomere repeats, and this proliferation-inhibition mechanism is defective in ALT cancer cells.
During transcription initiation, Ssl2, the dsDNA translocase of TFIIH, opens a 6-bp DNA bubble, suggesting a two-step model wherein Ssl2 triggers a 6-bp open complex that RNA polymerase II expands via NTP-dependent RNA transcription.
Cryo-EM analyses of human TRPML3 reveal this channel in three different states—closed, agonist-activated and low-pH-inhibited—and suggest mechanisms for regulation.
Engineering an LCK mutant, in which an active-site lysine is replaced by a photocaged equivalent via genetic code expansion, allows quantitation of phosphorylation kinetics in situ and provides insights into LCK activation dynamics.
