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News & Views |
DNA-binding proteins meet their mismatch
Mismatches are alterations in DNA that prevent the bases on each strand of the double helix from aligning correctly. It emerges that mismatches can bend DNA into favourable conformations for binding by proteins.
- Kale Kundert
- & James S. Fraser
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Article |
DNA mismatches reveal conformational penalties in protein–DNA recognition
A high-throughput assay that introduces mismatched base pairs into the DNA sequence shows that mismatches can increase transcription factor binding affinity by prepaying some of the energetic cost of distorting the DNA.
- Ariel Afek
- , Honglue Shi
- & Raluca Gordân
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News & Views |
Demystifying the D-loop during DNA recombination
Homologous recombination is a mechanism for DNA repair that enables the exchange of genetic information between DNA molecules. Structural analysis reveals how the protein RecA orchestrates this process.
- Upasana Roy
- & Eric C. Greene
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Article |
RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
Telomeric-repeat-containing RNA is recruited to telomeres by a mechanism that involves the DNA recombinase RAD51 and the formation of DNA–RNA hybrids, or R-loops—a process similar to that involved in homology-directed DNA repair.
- Marianna Feretzaki
- , Michaela Pospisilova
- & Joachim Lingner
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Article |
Mechanism of strand exchange from RecA–DNA synaptic and D-loop structures
Cryo-electron microscopy structures of the bacterial recombination protein RecA with DNA, and of RecA–D-loop complexes, provide insights into the double-stranded DNA opening, homology search and strand-exchange processes of homologous recombination.
- Haijuan Yang
- , Chun Zhou
- & Nikola P. Pavletich
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Article |
Innovations present in the primate interneuron repertoire
Single-nucleus RNA-sequencing analyses of brain from humans, macaques, marmosets, mice and ferrets reveal diverse ways that interneuron populations have changed during evolution.
- Fenna M. Krienen
- , Melissa Goldman
- & Steven A. McCarroll
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Article |
Repeat expansions confer WRN dependence in microsatellite-unstable cancers
In cells with microsatellite instability, expanded TA-dinucleotide repeats form cruciform structures that stall replication forks and cause chromosome shattering in the absence of the WRN helicase.
- Niek van Wietmarschen
- , Sriram Sridharan
- & André Nussenzweig
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Article |
Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B
Catalytically inactive DNMT3B3 is crucial in de novo CpG methylation of DNA, interacting with the nucleosome core to orient catalytically active DNMT3A2 so that it can bind to nearby linker DNA.
- Ting-Hai Xu
- , Minmin Liu
- & Peter A. Jones
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Article |
Bridging of DNA breaks activates PARP2–HPF1 to modify chromatin
The PARP2–HPF1 histone-modifying complex bridges two nucleosomes to align broken DNA ends for ligation, initiating conformational changes that activate PARP2 and enable DNA damage repair.
- Silvija Bilokapic
- , Marcin J. Suskiewicz
- & Mario Halic
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Article |
A protein assembly mediates Xist localization and gene silencing
A protein condensate formed by multivalent interactions between the long non-coding RNA Xist and specific RNA-binding proteins drives the compartmentalization required to perpetuate gene silencing on the inactive X chromosome.
- Amy Pandya-Jones
- , Yolanda Markaki
- & Kathrin Plath
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Article |
Identification of the human DPR core promoter element using machine learning
A machine learning approach shows that the downstream core promoter region (DPR) is widely used in human gene promoters, and that many promoters contain either a DPR or a TATA box, but not both.
- Long Vo ngoc
- , Cassidy Yunjing Huang
- & James T. Kadonaga
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Article |
The coding capacity of SARS-CoV-2
A high-resolution map of coding regions in the SARS-CoV-2 genome enables the identification of 23 unannotated open reading frames and quantification of the expression of canonical viral open reading frames.
- Yaara Finkel
- , Orel Mizrahi
- & Noam Stern-Ginossar
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Article |
C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance
Exposing Caenorhabditis elegans to non-coding small RNAs from pathogenic Pseudomonas aeruginosa induces avoidance behaviours in treated worms and their progeny, which reveals how C. elegans discriminates between bacterial species in its microbial environment.
- Rachel Kaletsky
- , Rebecca S. Moore
- & Coleen T. Murphy
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Article |
Epigenetic gene silencing by heterochromatin primes fungal resistance
Fission yeast grown in sublethal levels of caffeine develop heterochromatin-dependent epimutations conferring unstable heritable gene silencing that conveys resistance to caffeine, while remaining genetically wild type.
- Sito Torres-Garcia
- , Imtiyaz Yaseen
- & Robin C. Allshire
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News Feature |
The coronavirus is mutating — does it matter?
Different SARS-CoV-2 strains haven’t yet had a major impact on the course of the pandemic, but they might in future.
- Ewen Callaway
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Article |
Functionally uncoupled transcription–translation in Bacillus subtilis
In Bacillus subtilis, unlike in Escherichia coli, transcription and translation of genes are not tightly coupled, and pioneering ribosomes lag substantially behind RNA polymerases.
- Grace E. Johnson
- , Jean-Benoît Lalanne
- & Gene-Wei Li
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Article |
Regulation of the MLH1–MLH3 endonuclease in meiosis
Reconstitution of the activation of the MLH1–MLH3 endonuclease shows how crossovers are formed during meiosis.
- Elda Cannavo
- , Aurore Sanchez
- & Petr Cejka
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Article |
A single-cell transcriptome atlas of marsupial embryogenesis and X inactivation
Single-cell RNA-sequencing analysis of embryogenesis and X chromosome inactivation in the opossum (Monodelphis domestica) resolves the developmental trajectory of a marsupial, and sheds light on the evolution of embryogenesis in mammals.
- Shantha K. Mahadevaiah
- , Mahesh N. Sangrithi
- & James M. A. Turner
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Article |
PCNA activates the MutLγ endonuclease to promote meiotic crossing over
A new mechanism explaining how double Holliday junctions are specifically resolved into crossovers during meiosis is shown that resembles the initiation of DNA mismatch repair.
- Dhananjaya S. Kulkarni
- , Shannon N. Owens
- & Neil Hunter
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Article |
Structural basis for dimerization quality control
Structural studies of the dimerization quality control E3 ubiquitin ligase SCF–FBXL17 indicate that its selectivity for aberrant complex formation is based on recognizing both shape and complementarity of interacting domains.
- Elijah L. Mena
- , Predrag Jevtić
- & Michael Rape
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Article |
Dichotomous engagement of HDAC3 activity governs inflammatory responses
During the activation of mouse macrophages by lipopolysaccharides, histone deacetylase 3 controls inflammatory responses by both repressing and activating gene transcription depending on its differential association with transcription factors.
- Hoang C. B. Nguyen
- , Marine Adlanmerini
- & Mitchell A. Lazar
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Article |
Position-specific oxidation of miR-1 encodes cardiac hypertrophy
The 8-oxoguanine modification of the microRNA miR-1 results in redirected recognition and silencing of target genes and leads to cardiac hypertrophy in mice.
- Heeyoung Seok
- , Haejeong Lee
- & Sung Wook Chi
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Article |
Microbiota-derived metabolite promotes HDAC3 activity in the gut
Phytate metabolism and production of inositol trisphosphate by commensal bacteria activates epithelial histone deacetylase 3 and promotes intestinal repair.
- Shu-en Wu
- , Seika Hashimoto-Hill
- & Theresa Alenghat
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Article |
DNA targeting and interference by a bacterial Argonaute nuclease
Argonaute protein from the bacterium C. butyricum targets multicopy genetic elements and functions in the suppression of plasmid and phage propagation, and there appears to be a DNA-mediated immunity pathway in prokaryotes.
- Anton Kuzmenko
- , Anastasiya Oguienko
- & Andrey Kulbachinskiy
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Perspective |
Perspectives on ENCODE
The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.
- Federico Abascal
- , Reyes Acosta
- & Richard M. Myers
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Article
| Open AccessThe changing mouse embryo transcriptome at whole tissue and single-cell resolution
RNA expression is quantified at a tissue level in seventeen mouse tissues across embryonic development, and at the single-cell level in the developing limb.
- Peng He
- , Brian A. Williams
- & Barbara J. Wold
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Article
| Open AccessA large-scale binding and functional map of human RNA-binding proteins
A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.
- Eric L. Van Nostrand
- , Peter Freese
- & Gene W. Yeo
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Article
| Open AccessLandscape of cohesin-mediated chromatin loops in the human genome
A map of cohesin-mediated chromatin loops in 24 types of human cells identifies loops that show cell-type-specific variation, indicating that chromatin loops may help to specify cell-specific gene expression programs and functions.
- Fabian Grubert
- , Rohith Srivas
- & Michael Snyder
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Article |
MeCP2 links heterochromatin condensates and neurodevelopmental disease
The chromatin protein MeCP2 is a component of dynamic, liquid-like heterochromatin condensates, and the ability of MeCP2 to form condensates is disrupted by mutations in the MECP2 gene that occur in the neurodevelopmental disorder Rett syndrome.
- Charles H. Li
- , Eliot L. Coffey
- & Richard A. Young
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Article |
Histone H3.3 phosphorylation amplifies stimulation-induced transcription
The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.
- Anja Armache
- , Shuang Yang
- & Steven Z. Josefowicz
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Article |
SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation
Newly identified protein SPOCD1 is crucial in de novo DNA methylation directed by PIWI proteins and piRNAs, helping to control DNA silencing in mouse male germline.
- Ansgar Zoch
- , Tania Auchynnikava
- & Dónal O’Carroll
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Article |
Ageing hallmarks exhibit organ-specific temporal signatures
Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.
- Nicholas Schaum
- , Benoit Lehallier
- & Tony Wyss-Coray
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Article |
Nucleolar RNA polymerase II drives ribosome biogenesis
RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.
- Karan J. Abraham
- , Negin Khosraviani
- & Karim Mekhail
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Article |
N6-methyladenine in DNA antagonizes SATB1 in early development
The DNA modification N6-methyladenine regulates gene expression during mouse trophoblast development by depositing at the boundaries of active chromatin and preventing its spread by antagonizing the chromatin organizer SATB1.
- Zheng Li
- , Shuai Zhao
- & Andrew Z. Xiao
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Article |
Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
The E3 ubiquitin ligase TRIM7 polyubiquitinates the envelope protein of Zika virus, adding Lys63-linked polyubiquitin chains that interact with the TIM1 receptor of host cells to enhance virus entry and replication.
- Maria I. Giraldo
- , Hongjie Xia
- & Ricardo Rajsbaum
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Article |
Wapl repression by Pax5 promotes V gene recombination by Igh loop extrusion
Pax5 regulates contraction of the immunoglobulin heavy chain (Igh) locus—an essential step in V(D)J recombination—by promoting chromatin loop extrusion via repression of Wapl expression.
- Louisa Hill
- , Anja Ebert
- & Meinrad Busslinger
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Article |
Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading
Time-resolved cryogenic electron microscopy structures of a ribosome during the delivery of aminoacyl-tRNA by EF-Tu•GTP capture 33 ribosomal states, enabling visualization of the initial selection, proofreading and peptidyl transfer stages.
- Anna B. Loveland
- , Gabriel Demo
- & Andrei A. Korostelev
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News Round-Up |
Mathematical boycott, supercollider plan and lava-lamp cells
The latest science news, in brief.
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Article |
DNA surface exploration and operator bypassing during target search
Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.
- Emil Marklund
- , Brad van Oosten
- & Sebastian Deindl
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Article |
Pervasive lesion segregation shapes cancer genome evolution
Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity.
- Sarah J. Aitken
- , Craig J. Anderson
- & Martin S. Taylor
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Article |
Single-molecule imaging of transcription dynamics in somatic stem cells
Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.
- Justin C. Wheat
- , Yehonatan Sella
- & Ulrich Steidl
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News |
How cells’ ‘lava lamp’ effect could make cancer drugs more powerful
Discovery that synthetic compounds form concentrated droplets inside cells could shake up drug development — including the hunt for coronavirus treatments.
- Elie Dolgin
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Outlook |
Extracellular RNA
RNA is now known to travel outside cells to tissues around the body. Researchers are working out whether they can exploit this extracellular RNA to detect and treat disease.
- Herb Brody
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Outlook |
How extracellular vesicles can enhance drug delivery
In exosomes, our bodies have an efficient means of transmitting RNA information. Researchers want to use it to deliver drugs.
- Amanda B. Keener
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Outlook |
The biologist on the hunt for extracellular ribosomes
A serendipitous finding led Juan Pablo Tosar to uncover the protein-making machinery outside cells — a discovery that has scientists rethinking fundamental assumptions.
- Roxanne Khamsi
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Outlook |
Could tracking RNA in body fluids reveal disease?
Tests that detect extracellular RNA to spot cancer, heart disease and other conditions are in development.
- Elie Dolgin
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Outlook |
Dietary RNA is ripe for investigation
Kenneth Witwer says that RNA in food could have profound effects on the human digestive system and on health more generally.
- Kenneth Witwer
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Outlook |
Plant vesicles inspire methods to protect crops
Some studies have suggested that plants and fungi exchange RNA through extracellular vesicles. This has led some scientists to develop crop sprays that contain RNA.
- Roxanne Khamsi
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Article |
Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.
- Aldema Sas-Chen
- , Justin M. Thomas
- & Schraga Schwartz
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