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| 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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Article
| Open AccessRecA finds homologous DNA by reduced dimensionality search
Observations of rapid repair of double-stranded DNA breaks in sister choromosomes in Escherichia coli are consistent with a reduced-dimensionality-search model of RecA-mediated repair.
- Jakub Wiktor
- , Arvid H. Gynnå
- & Johan Elf
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Article |
Concerted cutting by Spo11 illuminates meiotic DNA break mechanics
A small proportion of Spo11-dependent DNA double-strand breaks are ‘double cuts’—adjacent breaks that occur in concert—revealing that gap repair during meiosis includes that of DNA gaps generated by Spo11 itself.
- Dominic Johnson
- , Margaret Crawford
- & Matthew J. Neale
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Article |
Spo11 generates gaps through concerted cuts at sites of topological stress
Meiotic recombination in yeast is not only initiated by single break sites, but also caused by closely spaced Spo11-dependent double-stranded DNA breaks that create chromosomal gaps.
- Silvia Prieler
- , Doris Chen
- & Franz Klein
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Article |
DNA-driven condensation assembles the meiotic DNA break machinery
During meiosis, Mer2 and the Rec114–Mei4 complex form condensates that facilitate the formation of double-strand DNA breaks by recruiting the Spo11 transesterase complex.
- Corentin Claeys Bouuaert
- , Stephen Pu
- & Scott Keeney
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Article |
Loop extrusion mediates physiological Igh locus contraction for RAG scanning
Long-distance V(D)J recombination is facilitated by contraction of the Igh locus and linear RAG scanning along chromatin, both driven by cohesin-mediated loop extrusion, which allows recombination of widely separated gene segments to occur.
- Hai-Qiang Dai
- , Hongli Hu
- & Frederick W. Alt
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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 |
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 |
Ensuring meiotic DNA break formation in the mouse pseudoautosomal region
In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X–Y recombination.
- Laurent Acquaviva
- , Michiel Boekhout
- & Scott Keeney
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Article |
Multilayered mechanisms ensure that short chromosomes recombine in meiosis
Several mechanisms regulate the distribution of double-strand breaks during meiosis in Saccharomyces cerevisiae, ensuring that the shortest chromosomes are able to successfully recombine.
- Hajime Murakami
- , Isabel Lam
- & Scott Keeney
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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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Article |
Extensive sex differences at the initiation of genetic recombination
Differential DNA methylation and the long-range effects of chromatin organization lead to pronounced differences in recombination landscape between males and females.
- Kevin Brick
- , Sarah Thibault-Sennett
- & Galina V. Petukhova
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Article |
Nuclear F-actin and myosins drive relocalization of heterochromatic breaks
Relocalization of heterochromatic double-strand breaks to the nuclear periphery in Drosophila cells occurs via directed motions driven by nuclear actin filaments and myosins activated by the Smc5/6 complex.
- Christopher P. Caridi
- , Carla D’Agostino
- & Irene Chiolo
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Article |
The transcription fidelity factor GreA impedes DNA break repair
In Escherichia coli, the control of RNA polymerase backtracking by transcription elongation factors impairs DNA break repair by affecting RecBCD resection and consequently RecA loading at sites far removed from the original DNA break.
- Priya Sivaramakrishnan
- , Leonardo A. Sepúlveda
- & Christophe Herman
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Letter |
Rad51-mediated double-strand break repair and mismatch correction of divergent substrates
DNA repair by break-induced replication begins with the Rad51-mediated invasion of single-stranded DNA into a double-stranded donor template; this study shows that successful recombination between highly mismatched substrates can occur when only five consecutive bases can be paired and that mismatch correction is most efficient near the invading end of the recipient strand.
- Ranjith Anand
- , Annette Beach
- & James Haber
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Letter |
Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function
An unexpected octameric integrase architecture for the betaretrovirus mouse mammary tumour virus intasome.
- Allison Ballandras-Colas
- , Monica Brown
- & Alan N. Engelman
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Letter |
Structural basis for retroviral integration into nucleosomes
Retroviruses such as HIV rely on the intasome, a tetramer of integrase protein bound to the viral DNA ends interacting with host chromatin, for integration into the host genome; the structure of the intasome as it interacts with a nucleosome is now solved, giving insight into the integration process.
- Daniel P. Maskell
- , Ludovic Renault
- & Peter Cherepanov
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Letter |
REV7 counteracts DNA double-strand break resection and affects PARP inhibition
Loss of REV7 is shown to regulate end resection of double-stranded DNA breaks in BRCA1-deficient cells, leading to PARP inhibitor resistance and restoration of homologous recombination; REV7 dictates pathway choice in BRCA1-deficient cells and during immunoglobulin class switching.
- Guotai Xu
- , J. Ross Chapman
- & Sven Rottenberg
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Letter |
Tel1ATM-mediated interference suppresses clustered meiotic double-strand-break formation
Meiotic recombination is initiated by a fairly uniform distribution of hundreds of DNA double-strand breaks catalysed by the Spo11 protein; here, Tel1 (orthologue of human ATM) is shown to be required for the localized inhibition that prevents double-strand breaks from forming close to one another.
- Valerie Garcia
- , Stephen Gray
- & Matthew J. Neale
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Letter |
Sae2 promotes dsDNA endonuclease activity within Mre11–Rad50–Xrs2 to resect DNA breaks
The MRX complex, required for double-strand break (DSB) repair by homologous recombination, has 3′ to 5′ exonuclease activity, but homologous recombination at a DSB uses a 3′-tailed molecule, which requires resection of the 5′ strand; here it is shown that in yeast, Sae2 nuclease promotes MRX to make an initial endonucleolytic cut on the 5′ strand that may allow MRX to digest the 5′ strand back to the end in a 3′ to 5′ fashion.
- Elda Cannavo
- & Petr Cejka
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Letter |
Transcript-RNA-templated DNA recombination and repair
Endogenous RNA transcripts are shown to mediate recombination with yeast chromosomal DNA; as the level of RNAs in the nucleus is quite high, these results may open up new understanding of the plasticity of repair and genome instability mechanisms.
- Havva Keskin
- , Ying Shen
- & Francesca Storici
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Letter |
BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks
Direct evidence for the role of BRCA1 in controlling homologous recombination at stalled replication forks has been obtained in mammalian cells using the bacterial Tus/Ter system.
- Nicholas A. Willis
- , Gurushankar Chandramouly
- & Ralph Scully
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Letter |
Structural basis for translocation by AddAB helicase–nuclease and its arrest at χ sites
A dual-function helicase–nuclease, typified by RecBCD in Escherichia coli, acts on free DNA ends during bacterial double-stranded break repair until it reaches a χ sequence at which it pauses before continuing with modified enzymatic properties; here several crystal structures of the related AddAB enzyme from Bacillus subtilis bound to χ-containing DNA are presented, offering insight into χ recognition and its effect on DNA translocation.
- Wojciech W. Krajewski
- , Xin Fu
- & Dale B. Wigley
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Letter |
RecA bundles mediate homology pairing between distant sisters during DNA break repair
RecA bundles are shown to be important for the pairing of homologous loci that have segregated to opposite ends of the cell during DNA double-strand break repair in vivo in Escherichia coli.
- Christian Lesterlin
- , Graeme Ball
- & David J. Sherratt
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Letter |
Meiotic chromosome structures constrain and respond to designation of crossover sites
Meiotic crossover regulation is proposed to operate as a self-limiting system in which meiotic chromosome structures create an environment that promotes crossovers, which in turn modify chromosome structures to inhibit crossover formation at additional neighbouring sites.
- Diana E. Libuda
- , Satoru Uzawa
- & Anne M. Villeneuve
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Letter |
Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration
This paper demonstrates that Pif1 helicase works with polymerase d to promote DNA synthesis through a migrating D-loop, a mechanism used to copy tens of kilobases during repair of chromosome breaks by break-induced replication (BIR).
- Marenda A. Wilson
- , YoungHo Kwon
- & Grzegorz Ira
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Letter |
HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis
Interstrand crosslink (ICL) repair involves proteins whose mutation results in the disorder Fanconi anaemia: here gene knockdown studies in mice show that the absence of HELQ, a protein previously implicated in ICL repair, compromises germ cell development and results in tumour predisposition due to defective recombination at damaged replication forks.
- Carrie A. Adelman
- , Rafal L. Lolo
- & Simon J. Boulton
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Article |
Pif1 family helicases suppress genome instability at G-quadruplex motifs
In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.
- Katrin Paeschke
- , Matthew L. Bochman
- & Virginia A. Zakian
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Letter |
Recombination-restarted replication makes inverted chromosome fusions at inverted repeats
A new mechanism of chromosomal rearrangement is identified through the observation that broken or collapsed DNA replication forks restarted by homologous recombination have a high propensity for U-turns at short inverted repeats; the error-prone nature of this mechanism is suggested to contribute to gross chromosomal rearrangements and copy-number variations present in cancer and other genomic disorders.
- Ken’Ichi Mizuno
- , Izumi Miyabe
- & Johanne M. Murray
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Letter |
Genetic recombination is directed away from functional genomic elements in mice
Comparison of Prdm9−/− and wild-type mice reveals a role for the PRDM9 protein in directing the recombination machinery away from important genomic regions.
- Kevin Brick
- , Fatima Smagulova
- & Galina V. Petukhova
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Letter |
Ecology drives a global network of gene exchange connecting the human microbiome
- Chris S. Smillie
- , Mark B. Smith
- & Eric J. Alm
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Article |
The landscape of recombination in African Americans
- Anjali G. Hinch
- , Arti Tandon
- & Simon R. Myers
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Letter |
Genome-wide analysis reveals novel molecular features of mouse recombination hotspots
- Fatima Smagulova
- , Ivan V. Gregoretti
- & Galina V. Petukhova
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Letter |
Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography
The E1 and E2 glycoproteins of alphaviruses form heterodimers and assemble into spikes on the virus surface, which mediate receptor binding and endocytosis. When the virion encounters acidic pH in the endosome E1 and E2 dissociate and E1 triggers fusion with the endosomal membrane. Two papers now provide the first crystal structures for glycoprotein complexes incorporating E2 at acidic and neutral pH, respectively. Together they provide insight into how fusion activation is controlled in alphaviruses.
- James E. Voss
- , Marie-Christine Vaney
- & Félix A. Rey
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Letter |
Fine-scale recombination rate differences between sexes, populations and individuals
Here, human genome-wide single-nucleotide polymorphism (SNP) data from more than 15,000 parent–offspring pairs have been used to construct the first recombination maps that are based on directly observed recombination events. The data reveal interesting differences between the sexes: for instance, in males recombination tends to shuffle exons, whereas in females it generates new combinations of nearby genes. Comparison of these maps with others also reveals population differences.
- Augustine Kong
- , Gudmar Thorleifsson
- & Kari Stefansson
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Letter |
xnd-1 regulates the global recombination landscape in Caenorhabditis elegans
To facilitate their proper segregation, duplicated meiotic chromosomes are physically joined by crossovers. Crossover formation begins with the introduction of meiosis-specific double-strand breaks. These authors identify a new gene in Caenorhabditis elegans, xnd-1, that is required for crossover distribution on both the X and the autosomal chromosomes. Preliminary data suggest that xnd-1 does this by regulating acetylation of histone H2A on lysine 5.
- Cynthia R. Wagner
- , Lynnette Kuervers
- & Judith L. Yanowitz
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News |
Virus-like particles speed bacterial evolution
The exchange of genetic information among ocean bacteria has been greatly underestimated.
- Amy Maxmen
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News & Views |
Common ancestry put to the test
The question of whether or not all life on Earth has an ultimate common origin is a subtle one, complicated by the phenomenon of lateral gene transfer. It has now been tackled with a formal statistical analysis.
- Mike Steel
- & David Penny