Featured
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Obituary |
Margarita Salas (1938–2019)
Biochemist whose discoveries led to faster, more-accurate DNA testing.
- Jesús Avila
- , Federico Mayor
- & Lourdes Ruiz-Desviat
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Article |
Key role for CTCF in establishing chromatin structure in human embryos
The chromatin regulator CTCF has key roles in the gradual development of hierarchical chromatin structure during human embryogenesis.
- Xuepeng Chen
- , Yuwen Ke
- & Zi-Jiang Chen
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Article |
The molecular landscape of ETMR at diagnosis and relapse
Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.
- Sander Lambo
- , Susanne N. Gröbner
- & Marcel Kool
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Article |
Regulation of α-synuclein by chaperones in mammalian cells
Chaperones interact with a canonical motif in α-synuclein, which can be prevented by phosphorylation of α-synuclein at Tyr39, whereas inhibition of this interaction leads to the localization of α-synuclein to the mitochondria and aggregate formation.
- Björn M. Burmann
- , Juan A. Gerez
- & Sebastian Hiller
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Article |
Developmental ROS individualizes organismal stress resistance and lifespan
A subpopulation of Caenorhabditis elegans, in which there is a naturally occurring transient increase in reactive oxygen species during early development, exhibits increased stress resistance, improved redox homeostasis and prolonged lifespan, which are linked to a global decrease in level of the histone mark H3K4me3.
- Daphne Bazopoulou
- , Daniela Knoefler
- & Ursula Jakob
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Article |
FACT caught in the act of manipulating the nucleosome
Two cryo-electron-microscopy images of the histone chaperone FACT interacting with components of nucleosomes shed light on how FACT manipulates nucleosomes to promote transcription, DNA repair and DNA replication.
- Yang Liu
- , Keda Zhou
- & Karolin Luger
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Article |
Chromatin structure dynamics during the mitosis-to-G1 phase transition
Analysis of the dynamics of chromosome reorganization after exit from mitosis reveals the distinct but mutually influential forces that drive chromatin reconfiguration.
- Haoyue Zhang
- , Daniel J. Emerson
- & Gerd A. Blobel
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Article |
Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM
Time-resolved electron microscopy reveals the mechanism by which the origin recognition complex loads pairs of MCM helicases around DNA prior to bidirectional replication.
- Thomas C. R. Miller
- , Julia Locke
- & Alessandro Costa
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Technology Feature |
Got mutation? ‘Base editors’ fix genomes one nucleotide at a time
A new class of CRISPR-based tools efficiently corrects point mutations in cell lines, animal models and perhaps the clinic.
- Sandeep Ravindran
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Article |
Dynamic lineage priming is driven via direct enhancer regulation by ERK
ERK reversibly regulates embryonic stem cell transcription via selective redistribution of co-factors and RNA polymerase from pluripotency to early differentiation enhancers, while leaving transcription factors bound to their enhancers, thus preserving plasticity.
- William B. Hamilton
- , Yaron Mosesson
- & Joshua M. Brickman
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Article |
Structure of the Fanconi anaemia monoubiquitin ligase complex
The structure of the multiprotein Fanconi anaemia core complex, determined using cryo-electron microscopy and mass spectrometry, shows that the complex adopts an extended asymmetric structure and highlights the structural and functional asymmetry of the RING finger domains.
- Shabih Shakeel
- , Eeson Rajendra
- & Lori A. Passmore
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Article |
Stabilization of chromatin topology safeguards genome integrity
Super-resolution microscopy demonstrates how changes in the 3D organization of chromatin protect DNA against excessive degradation following damage.
- Fena Ochs
- , Gopal Karemore
- & Claudia Lukas
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Article |
Metabolic regulation of gene expression by histone lactylation
The lactylation of lysine residues on histones in mammalian cells is stimulated by hypoxia and bacterial challenges, and increased histone lactylation induces genes involved in wound healing.
- Di Zhang
- , Zhanyun Tang
- & Yingming Zhao
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Article |
Alcohol metabolism contributes to brain histone acetylation
Acetate that is produced from the breakdown of alcohol contributes to histone acetylation in the brain, indicating that there is a direct link between alcohol metabolism and gene expression.
- P. Mews
- , G. Egervari
- & S. L. Berger
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Outlook |
How RNA therapies could be used to tackle the world’s biggest killer
Researchers hope that understanding the many roles of non-coding RNA in heart health and cardiovascular disease could deliver a therapeutic breakthrough.
- Chris Woolston
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Outlook |
The challenge of delivering RNA-interference therapeutics to their target cells
Delivery difficulties brought the nascent research field to its knees, but approval of the first RNA interference drug offers hope.
- Bianca Nogrady
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Article |
Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs
Gastrointestinal stromal tumours can be initiated by gain-of-function mutations of the KIT or PDGFRA oncogenes but also by loss of the metabolic complex succinate dehydrogenase (SDH), which leads to DNA hypermethylation; this study shows that in SDH-deficient tumours, displacement of CTCF insulators by DNA methylation activates oncogene expression, illustrating how epigenetic alterations can drive oncogenic signalling in the absence of kinase mutations.
- William A. Flavahan
- , Yotam Drier
- & Bradley E. Bernstein
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Article |
HP1 reshapes nucleosome core to promote phase separation of heterochromatin
The S. pombe HP1 protein Swi6 couples chromatin compaction to phase separation by dynamically exposing buried histone residues within nucleosomes.
- S. Sanulli
- , M. J. Trnka
- & G. J. Narlikar
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Article |
The ADP/ATP translocase drives mitophagy independent of nucleotide exchange
A CRISPR–Cas9 genetic screen shows that the adenine nucleotide translocator is required for mitophagy and that this role is independent of its nucleotide translocase activity.
- Atsushi Hoshino
- , Wei-jia Wang
- & Zoltan Arany
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News & Views |
The structure of DNA
In the early 1950s, the identity of genetic material was still a matter of debate. The discovery of the helical structure of double-stranded DNA settled the matter — and changed biology forever.
- Georgina Ferry
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Letter |
Spliceosomal disruption of the non-canonical BAF complex in cancer
A range of SF3B1 mutations promote tumorigenesis through the repression of BRD9, a core component of the non-canonical BAF complex, and correcting BRD9 mis-splicing in these SF3B1-mutant cells suppresses tumour growth.
- Daichi Inoue
- , Guo-Liang Chew
- & Robert K. Bradley
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Letter |
Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis
Analyses of transcriptomes from patients with acute myeloid leukaemia identified frequently co-occurring mutations of IDH2 and SRSF2, which functional analyses showed to have distinct and coordinated leukaemogenic effects on the epigenome and RNA splicing.
- Akihide Yoshimi
- , Kuan-Ting Lin
- & Omar Abdel-Wahab
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Letter |
eIF5B gates the transition from translation initiation to elongation
Single-molecule dynamics reveal that the GTPase activity of eukaryotic initiation factor eIF5B serves as a kinetic checkpoint for the transition from translation initiation to elongation.
- Jinfan Wang
- , Alex G. Johnson
- & Joseph D. Puglisi
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Letter |
The fundamental role of chromatin loop extrusion in physiological V(D)J recombination
V(D)J recombination in B cells involves cohesin-mediated extrusion of chromatin loops to present DNA targets for cleavage and joining.
- Yu Zhang
- , Xuefei Zhang
- & Frederick W. Alt
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Letter |
Genome architecture and stability in the Saccharomyces cerevisiae knockout collection
Whole-genome sequencing of the strains of the Saccharomyces cerevisiae gene-knockout collection reveals the effects of the deletion of non-essential genes on genome stability.
- Fabio Puddu
- , Mareike Herzog
- & Stephen P. Jackson
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Letter |
Structural basis of nucleosome recognition and modification by MLL methyltransferases
Cryo-electron microscopy structures of mixed-lineage leukaemia methyltransferases 1 and 3 associated with unmodified or mono-ubiquitinated nucleosome reveal the structural basis for the activity specificity and regulation of these enzymes.
- Han Xue
- , Tonghui Yao
- & Jing Huang
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Article |
A unified mechanism for intron and exon definition and back-splicing
The cryo-electron microscopy structures of an early spliceosome complex in yeast reveal a unified mechanism for defining introns and exons and also for back-splicing to generate circular RNA.
- Xueni Li
- , Shiheng Liu
- & Rui Zhao
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Letter |
Structures of influenza A virus RNA polymerase offer insight into viral genome replication
Structures of RNA polymerase of human and avian influenza A viruses reveal that the interface of the RNA polymerase dimer is required to initiate viral RNA synthesis in viral genome replication.
- Haitian Fan
- , Alexander P. Walker
- & Ervin Fodor
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Letter |
The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape
H3K36me2 targets DNMT3A to intergenic regions and this process, together with H3K36me3-mediated recruitment of DNMT3B, has a key role in establishing and maintaining genomic DNA methylation landscapes.
- Daniel N. Weinberg
- , Simon Papillon-Cavanagh
- & Chao Lu
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Outlook |
Cannabis’s chemical synergies
The notion of an ‘entourage effect’ that magnifies the drug’s effects is intriguing but lacks solid evidence.
- Tammy Worth
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Review Article |
Organization and regulation of gene transcription
Structural and microscopy studies of gene transcription underpin a model in which phosphorylation controls the shuttling of RNA polymerase II between promoter and gene-body condensates to regulate transcription initiation and elongation.
- Patrick Cramer
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Letter |
DEAD-box ATPases are global regulators of phase-separated organelles
RNA-dependent DEAD-box ATPases (DDXs) regulate the dynamics of phase-separated organelles, with ATP-bound DDXs promoting phase separation, and ATP hydrolysis inducing compartment disassembly and RNA release.
- Maria Hondele
- , Ruchika Sachdev
- & Karsten Weis
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Letter |
Insights into ubiquitin chain architecture using Ub-clipping
Enzymatic cleavage within ubiquitin molecules followed by quantitative mass-spectrometry simplifies complex ubiquitin chains and enables mapping of polyubiquitin architectures.
- Kirby N. Swatek
- , Joanne L. Usher
- & David Komander
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Letter |
BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells
The CTCF paralogue BORIS is upregulated in transcriptionally reprogrammed neuroblastoma cells rendered resistant to targeted therapy, in which it promotes regulatory chromatin interactions that maintain the resistance phenotype.
- David N. Debruyne
- , Ruben Dries
- & Rani E. George
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Letter |
Pol II phosphorylation regulates a switch between transcriptional and splicing condensates
RNA polymerase II with a hypophosphorylated C-terminal domain preferentially incorporates into mediator condensates, and with a hyperphosphorylated C-terminal domain into splicing-factor condensates, revealing phosphorylation as a regulatory mechanism in condensate preference.
- Yang Eric Guo
- , John C. Manteiga
- & Richard A. Young
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News & Views |
Yeast cells handle stress by reprogramming their metabolism
Stressed yeast cells take up the amino acid lysine and reprogram their metabolism to free up supplies of a stress-relieving molecule. Lysine uptake therefore increases the tolerance of yeast cells to stress.
- Jens Nielsen
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Review Article |
Advances in epigenetics link genetics to the environment and disease
The authors review recent advances and current debates in epigenetics, including how epigenetic mechanisms interact with genetic variation, ageing, disease and the environment.
- Giacomo Cavalli
- & Edith Heard
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Letter |
Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects
Single-cell RNA-sequencing analysis reveals functions of lineage-specifying transcription factors underlying congenital defects in heart development.
- T. Yvanka de Soysa
- , Sanjeev S. Ranade
- & Deepak Srivastava
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Letter |
Rotation tracking of genome-processing enzymes using DNA origami rotors
ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.
- Pallav Kosuri
- , Benjamin D. Altheimer
- & Xiaowei Zhuang
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Letter |
Non-photosynthetic predators are sister to red algae
Species of the eukaryotic phylum Rhodelphidia are non-photosynthetic, flagellate predators with gene-rich genomes, in contrast to their closely related sister lineage—the red algae—which are immotile, typically photoautotrophic and have relatively small intron-poor genomes and reduced metabolism.
- Ryan M. R. Gawryluk
- , Denis V. Tikhonenkov
- & Patrick J. Keeling
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Article |
Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy
A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.
- Jaecheol Lee
- , Vittavat Termglinchan
- & Joseph C. Wu
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Correspondence |
Engineered bacterium fuels evolution debate
- Patrick Forterre
- , Morgan Gaia
- & Da Cunha Violette
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Letter |
scSLAM-seq reveals core features of transcription dynamics in single cells
A technique known as scSLAM-seq that combines single-cell RNA sequencing with metabolic RNA labelling and nucleoside conversion is used to study the onset of cytomegalovirus infection in single mouse fibroblasts.
- Florian Erhard
- , Marisa A. P. Baptista
- & Lars Dölken
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Article |
Isomerization of BRCA1–BARD1 promotes replication fork protection
BRCA1–BARD1 has a role in replication fork protection that is mediated by a mechanism of phosphorylation-targeted isomerization of BRCA1 and is independent of the canonical interaction between BRCA1 and PALB2.
- Manuel Daza-Martin
- , Katarzyna Starowicz
- & Joanna R. Morris
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Article |
Developmental dynamics of lncRNAs across mammalian organs and species
A transcriptome dataset from seven organs and seven mammalian species throughout development is used to analyse the expression of long noncoding RNAs in tissues within and between species, and at different stages of organ development.
- Ioannis Sarropoulos
- , Ray Marin
- & Henrik Kaessmann
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Technology Feature |
Turning discarded DNA into ecology gold
Ecologists are monitoring biodiversity using DNA shed by wildlife into the environment.
- Sandeep Ravindran
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Research Highlight |
‘Microscope’ made of DNA reveals a cell’s hidden structures
DNA tags can be used to assemble a diagram of the genetic material inside a cell.
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News Feature |
The secret social lives of viruses
Scientists are listening in on the ways viruses communicate and cooperate. Decoding what the microbes are saying could be a boon to human health.
- Elie Dolgin
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News & Views |
Hijack of CRISPR defences by selfish genes holds clinical promise
Parasitic genetic elements called transposons carry CRISPR machinery that is normally used against them by bacterial cells. This paradox has now been explained, with implications for gene-therapy research.
- Fyodor D. Urnov
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