Mutagenesis articles within Nature Communications

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  • Article
    | Open Access

    Authors show that a common SNP upregulates endometrial Wnt4 expression and proimplantation genes in mouse proestrus and estrus. They suggest that this increases uterine permissiveness to embryo invasion, while decreasing resistance to invasion in reproductive cancers and endometriosis.

    • Mihaela Pavličev
    • , Caitlin E. McDonough-Goldstein
    •  & Louis Muglia

  • Article
    | Open Access

    Pathogenic variants of DDX3X are associated with neurodevelopmental disorders (NDD) and cancer. Here, the authors perform saturation genome editing of DDX3X to test the functional impact of 12,776 variants, develop a machine learning classifier to identify variants relevant for NDD, and show that DDX3X predominantly acts as a tumour suppressor in cancer.

    • Elizabeth J. Radford
    • , Hong-Kee Tan
    •  & Matthew E. Hurles

  • Article
    | Open Access

    The multiplex CRISPR system is the tool of choice for creating targeted tandemly arrayed genes (TAGs) deletions in plants. Here, the authors show that up to 80% of CRISPR-mediated TAG knockout alleles in Arabidopsis and rice are deletion-inversion bi-alleles, an unwanted products of targeted TAG deletions.

    • Jiuer Liu
    • , Feng-Zhu Wang
    •  & Jian-Feng Li

  • Article
    | Open Access

    Distinguishing the drivers of metastasis versus those of the primary tumour in breast cancer remains challenging. Here, the authors explore primary-only, metastatic-only, and shared drivers in breast cancer using mammary-specific transposon mutagenesis screens, which leads to potential therapeutic targets to prevent metastasis.

    • Zhe Jiang
    • , YoungJun Ju
    •  & Eldad Zacksenhaus

  • Article
    | Open Access

    TERT promoter mutations are the most common noncoding alterations in cancers, although some remain to be characterised. Here, the authors identify TERT promoter duplications across seven cancer types that are functionally equivalent to well-known hotspot TERT mutations and are clonal in a multifocal glioblastoma patient.

    • Carter J. Barger
    • , Abigail K. Suwala
    •  & Joseph F. Costello

  • Article
    | Open Access

    The successful use of CRISPR-based mutagenesis in non-conventional microorganisms requires high activity sgRNAs. Here, the authors present DeepGuide, a neural network-based architecture, that learns from genome-wide CRISPR activity profiles to accurately design Cas9 and Cas12a sgRNAs with high activity in the oleaginous yeast Yarrowia lipolytica.

    • Dipankar Baisya
    • , Adithya Ramesh
    •  & Ian Wheeldon

  • Article
    | Open Access

    What prevents a generalist predator from evolving and outperforming specialist predators? By combing analyses of natural variation with experimental evolution, Stewart et al. suggest that predator variation persists because most mutations have prey-specific effects, which results in relaxed selection

    • Balint Stewart
    • , Nicole Gruenheit
    •  & Christopher R. L. Thompson

  • Article
    | Open Access

    The glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting enzyme in the hexosamine pathway producing uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), an essential glycosylation precursor. Here, the authors dissect the mechanisms of GFAT-1 regulation by protein kinase A (PKA)-mediated phosphorylation.

    • Sabine Ruegenberg
    • , Felix A. M. C. Mayr
    •  & Martin S. Denzel

  • Article
    | Open Access

    The SRC Homology 3 (SH3) domains mediate protein–protein interactions (PPIs). Here, the authors assess the SH3-mediated PPIs in yeast, and show that the identity of the protein itself and the position of the SH3 both affect the interaction specificity and thus the PPI-dependent cellular functions.

    • Ugo Dionne
    • , Émilie Bourgault
    •  & Christian R. Landry

  • Article
    | Open Access

    The white pupae (wp) phenotype has been used for decades to selectively remove females of tephritid species in genetic sexing, but the determining gene is unknown. Here, the authors show that wp phenotype is produced by parallel mutations in a Major Facilitator Superfamily domain containing gene across multiple species.

    • Christopher M. Ward
    • , Roswitha A. Aumann
    •  & Marc F. Schetelig

  • Article
    | Open Access

    Deep learning models have shown great promise in predicting regulatory effects from DNA sequence. Here the authors evaluate sequence-based epigenomic deep learning models and conclude that these models are not yet ready to inform our knowledge of human disease.

    • Kushal K. Dey
    • , Bryce van de Geijn
    •  & Alkes L. Price

  • Article
    | Open Access

    Evidence that somatic mutation rates in introns exceed those in exons challenges the molecular evolution tenet that mutation rate and sequence function are independent. Here, authors analyze germline de novo mutations and reveal no evidence for mutation rate differences between exons and introns.

    • Miguel Rodriguez-Galindo
    • , Sònia Casillas
    •  & Antonio Barbadilla

  • Article
    | Open Access

    BRCA1 mutation carriers have higher chances of developing triple-negative breast cancer (TNBC). Here, the authors use the Sleeping Beauty mutagenesis system in Brca1 deficient mice and identify 169 putative driver genes, of which NOTCH1 accelerates TNBC formation through promoting epithelial-mesenchymal transition and cell cycle progression.

    • Kai Miao
    • , Josh Haipeng Lei
    •  & Chu-Xia Deng

  • Article
    | Open Access

    Although many neuropsychiatric risk genes are known to contribute to epigenetic regulation of gene expression, very little is known about specific chromatin-associated mechanisms that govern the formation and maintenance of neuronal connectivity. Here, the authors report that transcallosal connectivity is critically dependent on C11orf46/ARL14EP, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus, and that RNA-guided epigenetic editing of hyperexpressed Sema6a gene promoters in C11orf46-knockdown neurons resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling.

    • Cyril J. Peter
    • , Atsushi Saito
    •  & Atsushi Kamiya

  • Article
    | Open Access

    Interpreting genetic variation in the noncoding genome remains challenging, with functional effects difficult to predict. Here, the authors perform saturation mutagenesis combined with massively parallel reporter assays for 20 disease-associated regulatory elements, quantifying the effects of over 30,000 variants.

    • Martin Kircher
    • , Chenling Xiong
    •  & Nadav Ahituv

  • Article
    | Open Access

    Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

    • Andrew D. Johnston
    • , Claudia A. Simões-Pires
    •  & John M. Greally

  • Article
    | Open Access

    The role of mitochondrial DNA mutations in organismal fitness and lifespan have been studied in mitochondrial mutator models with varying results. Here, the authors generate a new APOBEC1 expression-based Drosophila mutator model and show that it has limited mitochondrial function and reduced lifespan.

    • Simonetta Andreazza
    • , Colby L. Samstag
    •  & Alexander J. Whitworth

  • Article
    | Open Access

    The SCRaMbLE system integrated into Sc2.0’s synthetic yeast chromosome project allows rapid strain evolution. Here the authors use a genetic logic gate to control induction of recombination in a haploid and diploid yeast carrying synthetic chromosomes.

    • Bin Jia
    • , Yi Wu
    •  & Ying-Jin Yuan

  • Article
    | Open Access

    High-throughput genetic screens in animals could benefit from an easy way to mark positive hits. Here the authors introduce photo-highlighting using a photoconvertible fluorescent protein, and in combination with stimulated Raman scattering (SRS) microscopy, define a role for BMP signaling in lipid metabolism in C. elegans.

    • Yong Yu
    • , Ayse Sena Mutlu
    •  & Meng C. Wang

  • Article
    | Open Access

    CRISPR-Cas9 screens are powerful high-throughput tools but can be confounded by nuclease toxicity. Here the authors design a library of variable length gRNAs with thousands of negative controls, including the targeting of ‘safe’ loci to account for on-target site DNA damage toxicity.

    • David W. Morgens
    • , Michael Wainberg
    •  & Michael C. Bassik

  • Article
    | Open Access

    Knockout collections provide a valuable tool to explore gene function, yet are expensive and technically challenging to produce at a genome-wide scale. Here Baym et al. devise a cost-effective transposon-based method to quickly develop a knockout collection for the electroactive microbe Shewanella oneidensis.

    • Michael Baym
    • , Lev Shaket
    •  & Buz Barstow

  • Article
    | Open Access

    Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

    • Paul K. Potter
    • , Michael R. Bowl
    •  & Steve D. M. Brown

  • Article
    | Open Access

    Plant-feeding insects of the Lygus genus have emerged as a major pest effecting cotton crops in the USA. Here the authors optimize the insecticidal activity of a Bacillus thuringiensis crystal protein and produce transgenic plants that are resistant to feeding damage by Lygusspecies.

    • Anilkumar Gowda
    • , Timothy J. Rydel
    •  & James A. Baum

  • Article
    | Open Access

    Mutational signatures provide evidence of the mechanism of action of a given mutagen and are found in cancer cells. Here, using 560 breast cancer genomes, the authors demonstrate that mutational signatures are frequently associated with genomic architecture including nucleosome positioning and replication timing.

    • Sandro Morganella
    • , Ludmil B. Alexandrov
    •  & Serena Nik-Zainal

  • Article
    | Open Access

    Inducing random mutation of C. elegansDNA is a widely used technique to investigate gene and protein function. Here the authors introduce a method of optogenetic mutagenesis, driving the generation of reactive oxygen species, which avoids the use of toxic chemicals.

    • Kentaro Noma
    •  & Yishi Jin

  • Article
    | Open Access

    Random DNA mutagenesis provides genetic diversity both in nature and the laboratory. Here, Badran and Liu present a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that surpasses the mutational efficiency and spectra of the most widely used in vivo and in vitromutagenesis methods.

    • Ahmed H. Badran
    •  & David R. Liu

  • Article |

    Microbial formate dehydrogenases (FDH) are molybdenum-containing enzymes that can catalyse the reduction of CO2 into formate. Here, the authors suggest a structural and functional basis for sulphuration of the molybdenum cofactor in E. coliFDH, a key step in the production of active formate dehydrogenase.

    • Pascal Arnoux
    • , Christian Ruppelt
    •  & Anne Walburger

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