X-chromosome inactivation draws L1 mutagenesis to the human X chromosome

X-chromosome inactivation (XCI) enables gene dosage compensation in XX eutherians. Long interspersed element-1 (LINE-1 or L1) retrotransposons are unusually abundant on the human X chromosome and are ...

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Laser phase plate improves structure determination of small proteins by cryo-EM

Phase plates can, in principle, overcome the poor image contrast in cryo–electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous de...

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Ancient wars between microbes gave us key immune defenses

A better understanding of battles between bacteria and viruses could inspire new medicines

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Human DHX29 detects nonoptimal codon usage to regulate mRNA stability

Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal codons are known to induce mRNA decay; however, the underlying molecular mechanism remains...

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Unstructured transcription factor interactions enable emergent specificity

How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), ...

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Structural modeling reveals phage proteins that manipulate bacterial immune signaling

Immune systems in animals, plants, and bacteria often rely on intracellular nucleotide signaling, which viruses can block by sequestering or degrading these signals. We identified structural and bioph...

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Evolution of error correction through a need for speed

Kinetic proofreading is a class of error-correcting mechanisms in biology that expend energy to avoid mistakes during replication, transcription, and translation. Proofreading is typically assumed to ...

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Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation

Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmica...

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Live-cell single-molecule dynamics of eukaryotic RNA polymerase machineries

Eukaryotic gene expression is orchestrated by RNA polymerases (RNAPI, II, and III) and associated factors, yet their real-time dynamics remain obscure. Using single-molecule tracking in living yeast, ...

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Programmable genome editing in human cells using RNA-guided bridge recombinases

Site-specific insertion of gene-sized DNA fragments remains an unmet need in the genome editing field. IS110-family serine recombinases have recently been shown to mediate programmable DNA recombinati...

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From sequence to function: Bridging single-molecule kinetics and molecular diversity

Biological function is fundamentally determined by nucleic acid and protein sequence. Beyond encoding genetic information, nucleic acids also display complex physicochemical parameters that shape stru...

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A genetically encoded device for transcriptome storage in mammalian cells

Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and s...

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Deep contrastive learning enables genome-wide virtual screening

Recent breakthroughs in protein structure prediction have opened new avenues for genome-wide drug discovery, yet existing virtual screening methods remain computationally prohibitive. We present DrugC...

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A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform

Mammalian SWI/SNF chromatin remodeling complexes modulate DNA accessibility and gene expression; however, their genomic targeting mechanisms remain incompletely understood. Here, we identify SWIFT (SW...

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Multistep genomics on single cells and live cultures in subnanoliter capsules

Single-cell sequencing methods uncover natural and induced variation between cells. Many functional genomic methods, however, require multiple steps that cannot yet be scaled to high throughput, inclu...

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Chromatin buffers torsional stress during transcription

During eukaryotic transcription, Pol II must overcome nucleosome obstacles and, because of DNA’s helical structure, must also rotate relative to DNA, generating torsional stress. However, there is lim...

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Chromothripsis and ecDNA initiated by N4BP2 nuclease fragmentation of cytoplasm-exposed chromosomes

Genome instability, including chromothripsis, is a hallmark of cancer. Cancer cells frequently contain micronuclei—small, nucleus-like structures formed by chromosome missegregation—that are susceptib...

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High-fidelity human chromosome transfer and elimination

The synthesis of human genomes and other gigabase-scale genomes will require new strategies. Here, we realized key steps in our pipeline for building synthetic human chromosomes. We established: (i) t...

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Cohesin guides homology search during DNA repair using loops and sister chromatid linkages

Accurate repair of DNA double-strand breaks (DSBs) is essential for genome stability, and defective repair underlies diseases such as cancer. Homologous recombination uses an intact homologous sequenc...

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Multiscale structure of chromatin condensates explains phase separation and material properties

The structure and interaction networks of molecules within biomolecular condensates are poorly understood. Using cryo–electron tomography and molecular dynamics simulations, we elucidated the structur...

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The evolving face of Science

Inspired by the redesign, our Design Managing Editor reviews covers across the course of Science’s 145-year legacy.

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