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News & Views |
A mechanism for inheriting radiation-induced DNA damage
Radiation-damaged paternal DNA has been found to cause embryos of the second generation of nematode worms, but not the first, to die. The proposed mechanisms help to explain the observed lack of such an effect in humans.
- Ronald Cutler
- & Jan Vijg
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Research Briefing |
Exploring the rapid evolution of the mammalian testis
The mammalian testis is a rapidly evolving organ, in both structural and molecular terms. An investigation of testicular cell nuclei from 11 species has unveiled genes, cell types and evolutionary forces that underlie these changes.
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Article |
R-loop-derived cytoplasmic RNA–DNA hybrids activate an immune response
RNA–DNA hybrids are immunogenic species that can aberrantly accumulate in the cytoplasm after R-loop processing, linking R-loop accumulation to cell death through the innate immune response.
- Magdalena P. Crossley
- , Chenlin Song
- & Karlene A. Cimprich
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Article
| Open AccessInheritance of paternal DNA damage by histone-mediated repair restriction
In Caenorhabditis elegans, paternal exposure to ionizing radiation results in HIS-24 and HPL-1-dependent genome instability phenotypes, causing embryonic lethality in the offspring.
- Siyao Wang
- , David H. Meyer
- & Björn Schumacher
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Article |
BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network
BRD8 is identified as a specific epigenetic vulnerability for glioblastomas that harbour wild-type p53.
- Xueqin Sun
- , Olaf Klingbeil
- & Alea A. Mills
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Article
| Open AccessThe molecular evolution of spermatogenesis across mammals
Evolutionary analyses of single-nucleus transcriptome data for testes from 11 species are reported, illuminating the molecular evolution of spermatogenesis and associated forces, and providing a resource for investigating the testis across mammals.
- Florent Murat
- , Noe Mbengue
- & Henrik Kaessmann
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Article |
A male germ-cell-specific ribosome controls male fertility
RibosomeST—a ribosome with a specialized nascent polypeptide exit tunnel—cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm.
- Huiling Li
- , Yangao Huo
- & Jiahao Sha
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Article |
Structural variants drive context-dependent oncogene activation in cancer
Results are presented that indicate that alterations to gene regulatory three-dimensional architecture are a critical mechanism that enables structural variant-based oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.
- Zhichao Xu
- , Dong-Sung Lee
- & Jesse R. Dixon
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Article
| Open AccessA transcriptional switch controls sex determination in Plasmodium falciparum
A non-genetic mechanism of sex determination in the human malaria parasite, Plasmodium falciparum, is described, and the male development 1 gene is identified as a potential target for interventions that block malaria transmission.
- A. R. Gomes
- , A. Marin-Menendez
- & A. M. Talman
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Article |
Microbial predators form a new supergroup of eukaryotes
Provora is an ancient supergroup of microbial predators that are genetically, morphologically and behaviourally distinct from other eukaryotes, and comprise two divergent clades of predators—Nebulidia and Nibbleridia—that differ fundamentally in ultrastructure, behaviour and gene content.
- Denis V. Tikhonenkov
- , Kirill V. Mikhailov
- & Patrick J. Keeling
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Article |
Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer
Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.
- Andrew L. H. Webster
- , Mathijs A. Sanders
- & Agata Smogorzewska
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Article
| Open AccessStructures of the holo CRISPR RNA-guided transposon integration complex
Structural studies of the CRISPR-associated transposon comprising Cas12k, TnsC, TnsB and TniQ from Scytonema hofmannii using cryo-electron microscopy reveal insights into the architecture and mechanism of RNA-guided DNA transposition.
- Jung-Un Park
- , Amy Wei-Lun Tsai
- & Elizabeth H. Kellogg
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Research Briefing |
How flowering plants compact their sperm DNA
It has not been clear how sperm DNA is compacted in the pollen of flowering plants. Research has now revealed that sperm chromatin, which is a complex of DNA and proteins, is packaged by a special histone protein that spontaneously aggregates in a phenomenon known as phase separation.
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Article
| Open AccessHistone H2B.8 compacts flowering plant sperm through chromatin phase separation
H2B.8 is identified as a histone variant that mediates a newly described mechanism of transcription-compatible chromatin condensation in flowering plant sperm cells.
- Toby Buttress
- , Shengbo He
- & Xiaoqi Feng
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News & Views |
Catching actin proteins in action
Two groups have visualized actin — the protein polymer that gives cells their shape — at high resolution. The structures provide in-depth views of the polymer as it adopts fleeting states and undergoes conformational changes.
- Pilar Cossio
- & Glen M. Hocky
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Article
| Open AccessSemi-automated assembly of high-quality diploid human reference genomes
Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.
- Erich D. Jarvis
- , Giulio Formenti
- & Karen H. Miga
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Article
| Open AccessStructure of the OMEGA nickase IsrB in complex with ωRNA and target DNA
The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.
- Seiichi Hirano
- , Kalli Kappel
- & Feng Zhang
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Article |
Programmable RNA sensing for cell monitoring and manipulation
RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.
- Yongjun Qian
- , Jiayun Li
- & Z. Josh Huang
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Article |
Structure of the NuA4 acetyltransferase complex bound to the nucleosome
The cryo-electron microscopy structure of NuA4 from Saccharomyces cerevisiae bound to the nucleosome illustrates how NuA4 is assembled and provides mechanistic insights into nucleosome recognition and transcription co-activation by a histone acetyltransferase.
- Keke Qu
- , Kangjing Chen
- & Zhucheng Chen
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Article |
A mechanism for oxidative damage repair at gene regulatory elements
The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.
- Swagat Ray
- , Arwa A. Abugable
- & Sherif F. El-Khamisy
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Article
| Open AccessVisualizing translation dynamics at atomic detail inside a bacterial cell
Cryo-electron tomography is used to reveal the structural dynamics and functional diversity of translating ribosomes in Mycoplasma pneumoniae, providing insight into the translation elongation cycle inside cells and how it is reshaped by antibiotics.
- Liang Xue
- , Swantje Lenz
- & Julia Mahamid
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News |
AlphaFold developers win US$3-million Breakthrough Prize
DeepMind’s system for predicting the 3D structure of proteins is among five recipients of science’s most lucrative awards.
- Zeeya Merali
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Article |
CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1
CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.
- Milan Hluchý
- , Pavla Gajdušková
- & Dalibor Blazek
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Article |
Glucose-driven TOR–FIE–PRC2 signalling controls plant development
Glucose signalling via TOR controls growth and differentiation through regulation of genome-wide histone methylation via FERTILIZATION-INDEPENDENT ENDOSPERM (FIE).
- Ruiqiang Ye
- , Meiyue Wang
- & Jen Sheen
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Article |
Columnar structure of human telomeric chromatin
Cryogenic electron microscopy analyses reveal a new, compact structure of telomeric chromatin, providing mechanistic insight into telomere maintenance and function.
- Aghil Soman
- , Sook Yi Wong
- & Lars Nordenskiöld
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Article
| Open AccessMechanism of AAA+ ATPase-mediated RuvAB–Holliday junction branch migration
Structures of the ATP-hydrolysing RuvAB complex captured in multiple conformations provide mechanistic insights into coordinated ATPase and motor activity during DNA recombination.
- Jiri Wald
- , Dirk Fahrenkamp
- & Thomas C. Marlovits
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Article |
Selective TnsC recruitment enhances the fidelity of RNA-guided transposition
CRISPR-associated transposons exploit a proofreading checkpoint to ensure high-fidelity selection of genomic sites for DNA insertion through specific recruitment of TnsC oligomers by the Cascade complex.
- Florian T. Hoffmann
- , Minjoo Kim
- & Samuel H. Sternberg
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Article
| Open AccessIn vivo single-molecule analysis reveals COOLAIR RNA structural diversity
The structures of single COOLAIR RNA isoforms change in abundance and shape in response to external conditions; structural mutation of these isoforms altered FLC expression and flowering time, consistent with a regulatory role of the COOLAIR structure in FLC transcription.
- Minglei Yang
- , Pan Zhu
- & Yiliang Ding
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Article
| Open AccessLive-seq enables temporal transcriptomic recording of single cells
Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy, can address a range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.
- Wanze Chen
- , Orane Guillaume-Gentil
- & Bart Deplancke
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News & Views |
Structural keys unlock RAS–MAPK cellular signalling pathway
Activation of the RAF protein is key to the RAS–MAPK signalling pathway, and involves the SMP protein complex. Structures for SMP shed light on the process, and suggest fresh targets for anticancer drug discovery.
- Hugo Lavoie
- & Marc Therrien
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Research Briefing |
A map of the human heart after myocardial infarction
Myocardial infarction, or heart attack, is one of the world’s biggest killers. An analysis of spatial and single-cell changes to human tissue after a heart attack provides insights into disease mechanisms and builds a resource for the discovery of therapeutics.
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Article |
Spatial multi-omic map of human myocardial infarction
A time-resolved high-resolution map of human cardiac remodelling after myocardial infarction, integrating single-cell transcriptomic, chromatin accessibility and spatial transcriptomic data, provides a valuable resource for the field.
- Christoph Kuppe
- , Ricardo O. Ramirez Flores
- & Rafael Kramann
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Article |
RNA editing underlies genetic risk of common inflammatory diseases
cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.
- Qin Li
- , Michael J. Gloudemans
- & Jin Billy Li
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Article |
Recording gene expression order in DNA by CRISPR addition of retron barcodes
Retro-Cascorder, a system for time-ordered recording of transcriptional output, uses retrons as a tag to mediate DNA barcode acquisition in a CRISPR array.
- Santi Bhattarai-Kline
- , Sierra K. Lear
- & Seth L. Shipman
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Review Article |
Inflammatory memory and tissue adaptation in sickness and in health
A Review on inflammatory memory in non-immune cells of different epithelia and neurons, and the potential mechanisms controlling these epigenetic memories and their implications in human health and disease.
- Shruti Naik
- & Elaine Fuchs
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Article
| Open AccessReconstitution of a telomeric replicon organized by CST
The Polα–primase-associated CST complex organizes telomeric C-strand DNA synthesis, and, in combination with telomerase, it carries out complete replication of the single-stranded DNA overhang found at human telomeres.
- Arthur J. Zaug
- , Karen J. Goodrich
- & Thomas R. Cech
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Article |
Structures of the human CST-Polα–primase complex bound to telomere templates
A structural analysis demonstrates how the single-stranded DNA-binding accessory protein complex CST physically organizes the human DNA polymerase-α–primase complex for efficient primer synthesis during telomere replication.
- Qixiang He
- , Xiuhua Lin
- & Ci Ji Lim
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Article |
Structure of Tetrahymena telomerase-bound CST with polymerase α-primase
Cryo-electron microscopy structures of Tetrahymena thermophila telomerase-bound Ctc1–Stn1–Ten1 and DNA polymerase α–primase provide insights into the molecular mechanisms underlying telomere replication and maintenance.
- Yao He
- , He Song
- & Juli Feigon
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Article
| Open AccessGTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins
The evolutionarily conserved RNA-binding protein GTSF1 and its homologues interact with members of the PIWI class of Argonaute proteins, increasing the efficiency of the RNA-cleaving activity of PIWI proteins, an essential function across the animal kingdom.
- Amena Arif
- , Shannon Bailey
- & Phillip D. Zamore
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Article
| Open AccessStructural insights into dsRNA processing by Drosophila Dicer-2–Loqs-PD
Structures of the Dcr-2–Loqs-PD complex while it is processing a double-stranded RNA (dsRNA) substrate elucidate the interactions between Dcr-2 and Loqs-PD, and show that Dcr-2 undergoes substantial conformational changes during a dsRNA-processing cycle.
- Shichen Su
- , Jia Wang
- & Jinbiao Ma
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Article
| Open AccessStructure of the Dicer-2–R2D2 heterodimer bound to a small RNA duplex
Cryo-electron microscopy structures of Drosophila Dicer-2–R2D2 complexes with and without small interfering RNA reveal how the RNA is presented to Argonaute in the correct orientation for viral gene silencing.
- Sonomi Yamaguchi
- , Masahiro Naganuma
- & Osamu Nureki
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Article |
Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy
- Mark Chaffin
- , Irinna Papangeli
- & Patrick T. Ellinor
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Article |
eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining
Single-molecule spectroscopy and structural studies were used to examine the dynamics of association of eIF1A and eIF5B with the human translation initiation complex and their role in presenting tRNA to the complex to initiate translation.
- Christopher P. Lapointe
- , Rosslyn Grosely
- & Joseph D. Puglisi
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Article |
cBAF complex components and MYC cooperate early in CD8+ T cell fate
cBAF is a negative determinant of memory T cell fate and the manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.
- Ao Guo
- , Hongling Huang
- & Douglas R. Green
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Article |
Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
Treatment with neoadjuvant BRAF/MEK-targeted therapy results in higher rates of major pathological response in female compared with male patients with melanoma, and pharmacological inhibition of androgen receptor signalling improved the responses of male and female mice to BRAF/MEK-targeted therapy.
- Christopher P. Vellano
- , Michael G. White
- & Jennifer A. Wargo
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Article
| Open AccessMechanism of replication origin melting nucleated by CMG helicase assembly
Cryo-electron microscopy structures of the sequential assembly of the CMG replicative helicase on a chromatinized origin of replication provide insights into the mechanism through which DNA melting is initiated by ATP binding.
- Jacob S. Lewis
- , Marta H. Gross
- & Alessandro Costa
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Matters Arising |
Limitations of gamete sequencing for crossover analysis
- Carl Veller
- , Shunxin Wang
- & Nancy Kleckner
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Research Briefing |
A hybrid control model for the eukaryotic cell cycle
The organizational principles of the eukaryotic cell cycle have yet to be pinned down, and two opposing models have been put forward. Genetic and proteomics analyses in a model eukaryote, fission yeast, reveal that the cell cycle is organized through a hybrid of both models, although the contribution of one strongly outweighs the other.
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Article
| Open AccessCohesin-mediated loop anchors confine the locations of human replication origins
A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.
- Daniel J. Emerson
- , Peiyao A. Zhao
- & Jennifer E. Phillips-Cremins
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