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Histone variant macroH2A1 represses gene expression in heterochromatin. New data show that it can also stimulate transcription by cooperating with PARP-1 to promote CBP-mediated H2B acetylation and that this regulatory function is lost in cancer cells.
Structural and biochemical analyses of full-length human BRCA2 reveal how it facilitates RAD51-mediated homologous recombination to repair DNA double-strand breaks.
Crystal structures of MhsT, a bacterial member of the neurotransmitter/sodium symporter family, in an occluded, inward-facing state with bound sodium and substrate reveal conformational changes during the transport cycle that provide new insights into the mechanism of cytoplasmic sodium release.
A genome-wide screen of gene targeting by an adeno-associated virus vector in human cells reveals that target sites are preferentially located where transcription occurs in the opposite direction from DNA replication, suggesting that colliding polymerases promote homologous recombination.
Crystal structures of the extracellular domain of human nAChR, in its apo form and with antagonists methyllycaconitine or α-bungarotoxin bound, are presented. The structures provide insight into the channel-opening mechanism of nAChRs and their pharmacological properties.
The RNA-binding protein Rbfox is an established regulator of alternative splicing. Here, Kawamoto and colleagues identify transcriptome-wide targets of Rbfox3 in neuronal cells and tissues to uncover an unexpected role in pri-miRNA processing
New in vivo analyses in Schizosaccharomyces pombe suggest that the RNA exosome promotes transcription termination by targeting the 3' end of nascent transcripts associated with 'backtracked' RNA polymerase II, revealing a new link between mRNA surveillance and termination.
Chemotherapeutic drug Gleevec (imatinib) is a potent and specific inhibitor of Abl kinase. NMR and fast kinetic analyses now reveal that Abl undergoes an induced-fit conformational change upon Gleevec binding.
A solution NMR structure of the pre-mRNA retention and splicing (RES) core complex from budding yeast now reveals how the trimer stabilizes the RRM of its Snu17 subunit to promote pre-mRNA interactions within the spliceosome.
New single-molecule imaging analyses reveal how dynamic interactions of RPA, Rad52 and Rad51 on single-stranded DNA direct assembly of the presynaptic complex that promotes strand invasion during homologous recombination.
A combination of two-dimensional gel electrophoresis and EM is used to isolate and characterize multiple template-switching intermediates generated in budding yeast during replication of damaged DNA.
A single-molecule optical-trapping approach is used to examine protein unfolding and translocation by double-ring AAA+ machine ClpA. Although ClpA can unfold some substrates faster than ClpX can, it translocates the unfolded polypeptide more slowly.
The crystal structure of a human cohesin subcomplex, SA2–Scc1, guides mutagenesis analyses to dissect the antagonistic roles of shugoshin and Wapl in regulating centromeric functions during mitosis.
The protein TRIM28 is identified as a factor that modulates RNA polymerase II pausing and transcriptional elongation at a large number of mammalian genes. This function is regulated by transcription-coupled phosphorylation of TRIM28 at Ser824.
Analyses of transcription and chromatin states during the yeast metabolic cycle reveal the links between different chromatin modifications and gene expression. The data also show that chromatin-modifier occupancies do not precisely match modification patterns.
Cancer cells lacking telomerase maintain telomere lengths required for cell growth through a recombination mechanism called ALT. Now, ALT-specific nuclear receptors are shown to recruit a zinc-finger protein that directs the nucleosome remodeler and histone deacetylase NuRD to telomeres to enhance homologous recombination.
Alternative pre-mRNA splicing is often jointly controlled by multiple splicing factors. Here Muto and colleagues elucidate the structural basis for cooperative RNA recognition by two splicing regulators required for tissue-specific expression of C. elegans FGFR.
High-resolution structures of the 70S ribosome from Thermus thermophilus reveal a network of ordered waters in the peptidyl transferase center that suggests a mechanism for proton movement and formation and breakdown of the tetrahedral intermediate.
Chemical cross-linking MS and supporting biochemical and genetic analyses reveal the architecture of the yeast Core Factor complex and suggest how it directs transcription of RNA Pol I at rDNA promoters.
Type I CRISPR-Cas systems require a target-searching Cascade complex and the Cas3 degradation machine to drive prokaryotic adaptation to alien nucleic acids. Cas3 crystal structures now reveal the mechanism of concerted DNA unwinding and degradation.