Molecular biology

  • Article
    | Open Access

    The Lys48-linked polyubiquitin-mediated proteasomal degradation in yeast depends on Cdc48 and its cofactors Ufd1 and Npl4. Here, the authors present crystal structures of Npl4 bound to Lys48-linked diubiquitin and the Npl4-binding motif of Ufd1, providing insights into the reaction mechanism of the Cdc48- Ufd1/Npl4 complex.

    • Yusuke Sato
    • , Hikaru Tsuchiya
    • , Atsushi Yamagata
    • , Kei Okatsu
    • , Keiji Tanaka
    • , Yasushi Saeki
    •  & Shuya Fukai
  • Article
    | Open Access

    The BEN-solo proteins—including Insensitive (Insv), Elba1 and Elba2—function in both transcriptional repression and chromatin insulation. Here, the authors investigate the role of these proteins in Drosophila embryos, finding that ELBA and Insv function as general insulators and partition active chromatin to ensure proper gene activation in Drosophila.

    • Malin Ueberschär
    • , Huazhen Wang
    • , Chun Zhang
    • , Shu Kondo
    • , Tsutomu Aoki
    • , Paul Schedl
    • , Eric C. Lai
    • , Jiayu Wen
    •  & Qi Dai
  • Article
    | Open Access

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    The design of protein assemblies is a major thrust for biomolecular engineering and nanobiotechnology. Here the authors demonstrate a general mechanism for designing allosteric macromolecular assemblies and showcase a proof of concept for engineered allosteric protein assembly.

    • Luis A. Campos
    • , Rajendra Sharma
    • , Sara Alvira
    • , Federico M. Ruiz
    • , Beatriz Ibarra-Molero
    • , Mourad Sadqi
    • , Carlos Alfonso
    • , Germán Rivas
    • , Jose M. Sanchez-Ruiz
    • , Antonio Romero Garrido
    • , José M. Valpuesta
    •  & Victor Muñoz
  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    miRNA142-3p and Tet2 are separately known to regulate Treg. Here the authors show that miRNA142-3p targets Tet2 and by this opposes Treg differentiation in autoimmune diabetes.

    • Martin G. Scherm
    • , Isabelle Serr
    • , Adam M. Zahm
    • , Jonathan Schug
    • , Saverio Bellusci
    • , Rossella Manfredini
    • , Victoria K. Salb
    • , Katharina Gerlach
    • , Benno Weigmann
    • , Anette-Gabriele Ziegler
    • , Klaus H. Kaestner
    •  & Carolin Daniel
  • Article
    | Open Access

    Common Fragile Sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Here the authors use genome-wide and single cell techniques to assess how replication timing and transcriptional activity correlate with genome stability.

    • Olivier Brison
    • , Sami El-Hilali
    • , Dana Azar
    • , Stéphane Koundrioukoff
    • , Mélanie Schmidt
    • , Viola Nähse
    • , Yan Jaszczyszyn
    • , Anne-Marie Lachages
    • , Bernard Dutrillaux
    • , Claude Thermes
    • , Michelle Debatisse
    •  & Chun-Long Chen
  • Article
    | Open Access

    Although many species-specific imprinted genes have been identified, how the evolutionary switch from biallelic to imprinted expression occurs is still unknown. Here authors find that lineage-specific ERVs active as oocyte promoters can induce de novo DNA methylation at gDMRs and imprinting.

    • Aaron B. Bogutz
    • , Julie Brind’Amour
    • , Hisato Kobayashi
    • , Kristoffer N. Jensen
    • , Kazuhiko Nakabayashi
    • , Hiroo Imai
    • , Matthew C. Lorincz
    •  & Louis Lefebvre
  • Article
    | Open Access

    Primary cilia have been proposed to regulate glucose metabolism and insulin secretion in beta cells, but it is not known how. Here the authors show that primary cilia play a role in adult β-cell function via a mechanism involving endosomal EphA-processing.

    • Francesco Volta
    • , M. Julia Scerbo
    • , Anett Seelig
    • , Robert Wagner
    • , Nils O’Brien
    • , Felicia Gerst
    • , Andreas Fritsche
    • , Hans-Ulrich Häring
    • , Anja Zeigerer
    • , Susanne Ullrich
    •  & Jantje M. Gerdes
  • Article
    | Open Access

    Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.

    • Osamu Iwasaki
    • , Hideki Tanizawa
    • , Kyoung-Dong Kim
    • , Andrew Kossenkov
    • , Timothy Nacarelli
    • , Sanki Tashiro
    • , Sonali Majumdar
    • , Louise C. Showe
    • , Rugang Zhang
    •  & Ken-ichi Noma
  • Article
    | Open Access

    Single-molecule in vitro assays require dedicated confocal microscopes equipped with fluorescence correlation spectroscopy (FCS) modules. Here the authors present a compact, cheap and open-source 3D-printed confocal microscope for single photon counting and FCS measurements, and use it to detect α-synuclein aggregation.

    • James W. P. Brown
    • , Arnaud Bauer
    • , Mark E Polinkovsky
    • , Akshay Bhumkar
    • , Dominic J. B. Hunter
    • , Katharina Gaus
    • , Emma Sierecki
    •  & Yann Gambin
  • Article
    | Open Access

    XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X chromosome inactivation. Here, the authors investigate TEs associated with the XACT locus and identify a critical enhancer for its regulation, which evolved from an ancestral group of mammalian endogenous retroviruses, prior to the emergence of XACT.

    • Miguel Casanova
    • , Madeleine Moscatelli
    • , Louis Édouard Chauvière
    • , Christophe Huret
    • , Julia Samson
    • , Tharvesh Moideen Liyakat Ali
    • , Olga Rosspopoff
    •  & Claire Rougeulle
  • Article
    | Open Access

    Engineered biological nanopores enable observation of single molecule chemistry events; however a cylindrical pore geometry can have undesired effects. The authors report a conical biological pore which was embedded with tetrachloroaurate(III) to allow for discrimination between different biothiols.

    • Jiao Cao
    • , Wendong Jia
    • , Jinyue Zhang
    • , Xiumei Xu
    • , Shuanghong Yan
    • , Yuqin Wang
    • , Panke Zhang
    • , Hong-Yuan Chen
    •  & Shuo Huang
  • Article
    | Open Access

    While the cellular recycling process autophagy has been linked to aging, the impact of selective autophagy on lifespan remains unclear. Here Kumsta et al. show that the autophagy receptor p62/SQSTM1 is required for hormetic benefits and p62/SQSTM1 overexpression is sufficient to extend C. elegans lifespan and improve proteostasis.

    • Caroline Kumsta
    • , Jessica T. Chang
    • , Reina Lee
    • , Ee Phie Tan
    • , Yongzhi Yang
    • , Rute Loureiro
    • , Elizabeth H. Choy
    • , Shaun H. Y. Lim
    • , Isabel Saez
    • , Alexander Springhorn
    • , Thorsten Hoppe
    • , David Vilchez
    •  & Malene Hansen
  • Article
    | Open Access

    Artificial nanopores can perform selective gating of molecules analogous to transmembrane proteins. Here, the authors design a DNA origami pore with a controllable lid for size-selective gating and translocation of macromolecules and evaluate its biosensing properties by single particle assay.

    • Rasmus P. Thomsen
    • , Mette Galsgaard Malle
    • , Anders Hauge Okholm
    • , Swati Krishnan
    • , Søren S.-R. Bohr
    • , Rasmus Schøler Sørensen
    • , Oliver Ries
    • , Stefan Vogel
    • , Friedrich C. Simmel
    • , Nikos S. Hatzakis
    •  & Jørgen Kjems
  • Article
    | Open Access

    PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.

    • Jerry H. Houl
    • , Zu Ye
    • , Chris A. Brosey
    • , Lakshitha P. F. Balapiti-Modarage
    • , Sarita Namjoshi
    • , Albino Bacolla
    • , Daniel Laverty
    • , Brian L. Walker
    • , Yasin Pourfarjam
    • , Leslie S. Warden
    • , Naga Babu Chinnam
    • , Davide Moiani
    • , Roderick A. Stegeman
    • , Mei-Kuang Chen
    • , Mien-Chie Hung
    • , Zachary D. Nagel
    • , Tom Ellenberger
    • , In-Kwon Kim
    • , Darin E. Jones
    • , Zamal Ahmed
    •  & John A. Tainer
  • Article
    | Open Access

    Long primary transcripts of microRNAs are co-transcriptionally cleaved by the enzyme Drosha. Here the authors suggest that DNA methylation in miRNA loci in mammalian cells increases Drosha binding, slowing RNA polymerase II elongation to enhance miRNA biogenesis.

    • Ohad Glaich
    • , Shivang Parikh
    • , Rachel E. Bell
    • , Keren Mekahel
    • , Maya Donyo
    • , Yodfat Leader
    • , Ronna Shayevitch
    • , Danna Sheinboim
    • , Sivan Yannai
    • , Dror Hollander
    • , Ze’ev Melamed
    • , Galit Lev-Maor
    • , Gil Ast
    •  & Carmit Levy
  • Article
    | Open Access

    It was known that prolonged TRMPL1 activation induces TFEB translocation and upregulates autophagic gene regulation. Here, the authors show that acute TRMPL1 activation also induces autophagy through VPS34 and by lysosomal calcium release independent of TFEB.

    • A. Scotto Rosato
    • , S. Montefusco
    • , C. Soldati
    • , S. Di Paola
    • , A. Capuozzo
    • , J. Monfregola
    • , E. Polishchuk
    • , A. Amabile
    • , C. Grimm
    • , A. Lombardo
    • , M. A. De Matteis
    • , A. Ballabio
    •  & D. L. Medina
  • Article
    | Open Access

    Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.

    • Lena Lampe
    • , Marius Jentzsch
    • , Sylwia Kierszniowska
    •  & Elena A. Levashina
  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    • , Vasavi Sundaram
    •  & Ting Wang
  • Article
    | Open Access

    Polymorphisms in LMO1 are associated with increased susceptibility to develop neuroblastoma. Here, the authors show that LMO1 directly induces the transcription factor ASCL1, which regulates the differentiation of neurons, demonstrating that ASCL1 is part of the adrenergic neuroblastoma core regulatory circuit.

    • Lu Wang
    • , Tze King Tan
    • , Adam D. Durbin
    • , Mark W. Zimmerman
    • , Brian J. Abraham
    • , Shi Hao Tan
    • , Phuong Cao Thi Ngoc
    • , Nina Weichert-Leahey
    • , Koshi Akahane
    • , Lee N. Lawton
    • , Jo Lynne Rokita
    • , John M. Maris
    • , Richard A. Young
    • , A. Thomas Look
    •  & Takaomi Sanda
  • Article
    | Open Access

    The mRNA-surveillance pathway of no-go decay (NGD) is a eukaryotic ribosome-based-quality-control process that targets transcripts that stall the ribosome. Here the authors show no-go decay (NGD) and ribosome-quality control (RQC) pathways are activated by mRNAs damaged by alkylation and oxidation stress.

    • Liewei L. Yan
    • , Carrie L. Simms
    • , Fionn McLoughlin
    • , Richard D. Vierstra
    •  & Hani S. Zaher
  • Article
    | Open Access

    Bacterial tRNA is modified by thiolation of nucleosides. Here the authors identify 2-methylthiocytidine in bacterial tRNA using nucleic acid isotope labeling coupled mass spectrometry. Exposure to methylating agents converts 2-thiocytidine to 2-methylthiocytidine, which is repaired by demethylase AlkB in vivo.

    • Valentin F. Reichle
    • , Dimitar P. Petrov
    • , Verena Weber
    • , Kirsten Jung
    •  & Stefanie Kellner
  • Article
    | Open Access

    Class 1 CRISPR systems are not as developed for genome editing as Class 2 systems are. Here the authors show that Cas3 can be used to generate functional knockouts and knock-ins, as well as Cas3-mediated exon-skipping in DMD cells.

    • Hiroyuki Morisaka
    • , Kazuto Yoshimi
    • , Yuya Okuzaki
    • , Peter Gee
    • , Yayoi Kunihiro
    • , Ekasit Sonpho
    • , Huaigeng Xu
    • , Noriko Sasakawa
    • , Yuki Naito
    • , Shinichiro Nakada
    • , Takashi Yamamoto
    • , Shigetoshi Sano
    • , Akitsu Hotta
    • , Junji Takeda
    •  & Tomoji Mashimo
  • Article
    | Open Access

    Current methods to measure extracellular pH are often limited in resolution and response times. Here the authors present a label-free nanoprobe, consisting of a zwitterionic nanomembrane at the tip of a nanopipette, which enables high spatiotemporal resolution pH measurements and topography-pH 3D mapping in live cancer cells.

    • Yanjun Zhang
    • , Yasufumi Takahashi
    • , Sung Pil Hong
    • , Fengjie Liu
    • , Joanna Bednarska
    • , Philip S. Goff
    • , Pavel Novak
    • , Andrew Shevchuk
    • , Sahana Gopal
    • , Iros Barozzi
    • , Luca Magnani
    • , Hideki Sakai
    • , Yoshimoto Suguru
    • , Takuto Fujii
    • , Alexander Erofeev
    • , Peter Gorelkin
    • , Alexander Majouga
    • , Dominik J. Weiss
    • , Christopher Edwards
    • , Aleksandar P. Ivanov
    • , David Klenerman
    • , Elena V. Sviderskaya
    • , Joshua B. Edel
    •  & Yuri Korchev
  • Article
    | Open Access

    During meiosis, pairing of homologous chromosomes is critical for sexual reproduction. Here the authors reveal in S. pombe the role of lncRNA–protein complexes during the pairing of homologues chromosomes that assemble at specific chromosomal loci to mediate recognition of the pairs.

    • Da-Qiao Ding
    • , Kasumi Okamasa
    • , Yuki Katou
    • , Eriko Oya
    • , Jun-ichi Nakayama
    • , Yuji Chikashige
    • , Katsuhiko Shirahige
    • , Tokuko Haraguchi
    •  & Yasushi Hiraoka
  • Article
    | Open Access

    Senescence of metabolically active cells is a process linked to ageing. Here the authors reveal that CSB is required to block replicative senescence, and epigenetic control of CSB downregulation triggers proliferative arrest in a p21-dependent manner.

    • Clément Crochemore
    • , Cristina Fernández-Molina
    • , Benjamin Montagne
    • , Audrey Salles
    •  & Miria Ricchetti
  • Article
    | Open Access

    E. coli and human tRNAs contain 3-(3-amino-3-carboxypropyl)uridine (acp3U) modification. Here the authors identify E. coli TapT and human DTWD1/2 as tRNA aminocarboxypropyltransferases responsible for acp3U formation. Inhibition of acp3U modification results in genome instability in heat-stressed E. coli and growth defects in human cells.

    • Mayuko Takakura
    • , Kensuke Ishiguro
    • , Shinichiro Akichika
    • , Kenjyo Miyauchi
    •  & Tsutomu Suzuki
  • Article
    | Open Access

    MLL family histone methyltransferases deposit histone H3 Lys4 mono-/di-/tri-methylation and regulate gene expression in mammals. Here the authors report the single-particle cryo-EM structure of the NCP-bound human MLL1 core complex, shedding light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

    • Sang Ho Park
    • , Alex Ayoub
    • , Young-Tae Lee
    • , Jing Xu
    • , Hanseong Kim
    • , Wei Zheng
    • , Biao Zhang
    • , Liang Sha
    • , Sojin An
    • , Yang Zhang
    • , Michael A. Cianfrocco
    • , Min Su
    • , Yali Dou
    •  & Uhn-Soo Cho
  • Article
    | Open Access

    RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.

    • Yashar Sadian
    • , Florence Baudin
    • , Lucas Tafur
    • , Brice Murciano
    • , Rene Wetzel
    • , Felix Weis
    •  & Christoph W. Müller
  • Article
    | Open Access

    Bacteria use CRISPR-Cas systems to protect themselves against viral infections. Here, Watson et al. show that a type I CRISPR-Cas system can induce abortive viral infection, where infected cells do not survive but viral propagation is decreased, thus protecting the bacterial population.

    • Bridget N. J. Watson
    • , Reuben B. Vercoe
    • , George P. C. Salmond
    • , Edze R. Westra
    • , Raymond H. J Staals
    •  & Peter C. Fineran
  • Article
    | Open Access

    Avian influenza A virus (IAV) strains replicate poorly in mammalian hosts, but mechanisms underlying species restriction are incompletely understood. Here, Bogdanow et al. show that avian and mammalian adapted IAV strains have evolved different RNA structure features for regulation of M segment RNA splicing.

    • Boris Bogdanow
    • , Xi Wang
    • , Katrin Eichelbaum
    • , Anne Sadewasser
    • , Immanuel Husic
    • , Katharina Paki
    • , Matthias Budt
    • , Martha Hergeselle
    • , Barbara Vetter
    • , Jingyi Hou
    • , Wei Chen
    • , Lüder Wiebusch
    • , Irmtraud M. Meyer
    • , Thorsten Wolff
    •  & Matthias Selbach
  • Article
    | Open Access

    The off-target effects and on-target mutations of CRISPR editing in higher non-human primates are complex. Here the authors perform whole genome trio sequencing of rhesus monkeys and see no unexpected mutations.

    • Xin Luo
    • , Yaoxi He
    • , Chao Zhang
    • , Xiechao He
    • , Lanzhen Yan
    • , Min Li
    • , Ting Hu
    • , Yan Hu
    • , Jin Jiang
    • , Xiaoyu Meng
    • , Weizhi Ji
    • , Xudong Zhao
    • , Ping Zheng
    • , Shuhua Xu
    •  & Bing Su
  • Article
    | Open Access

    CRISPR-Cas systems have well characterized, modular structures. Here the authors use that architecture to design a Cas12a library of 560 synthetic chimeras, with altered PAM preferences and specificities.

    • R. M. Liu
    • , L. L. Liang
    • , E. Freed
    • , H. Chang
    • , E. Oh
    • , Z. Y. Liu
    • , A. Garst
    • , C. A. Eckert
    •  & R. T. Gill
  • Article
    | Open Access

    Mutation of the nuclear envelope protein, barrier-to-autointegration factor 1 (Banf1), has previously been associated with the development of ageing associated diseases in a human progeria syndrome. Here, the authors reveal the functional link between Banf1-regulated, PARP1-directed repair of oxidative lesions.

    • Emma Bolderson
    • , Joshua T. Burgess
    • , Jun Li
    • , Neha S. Gandhi
    • , Didier Boucher
    • , Laura V. Croft
    • , Samuel Beard
    • , Jennifer J. Plowman
    • , Amila Suraweera
    • , Mark N. Adams
    • , Ali Naqi
    • , Shu-Dong Zhang
    • , David A. Sinclair
    • , Kenneth J. O’Byrne
    •  & Derek J. Richard
  • Article
    | Open Access

    Major effect loci controlling natural, heritable variation in telomere length are not known. Here, the authors use QTL mapping and transgenic manipulations in Arabidopsis to implicate the rRNA-processing genes NOP2A and RPL5 in telomere length set point regulation in this model species.

    • Liliia R. Abdulkina
    • , Callie Kobayashi
    • , John T. Lovell
    • , Inna B. Chastukhina
    • , Behailu B. Aklilu
    • , Inna A. Agabekian
    • , Ana V. Suescún
    • , Lia R. Valeeva
    • , Chuluuntsetseg Nyamsuren
    • , Galina V. Aglyamova
    • , Margarita R. Sharipova
    • , Dorothy E. Shippen
    • , Thomas E. Juenger
    •  & Eugene V. Shakirov
  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    • , Yongge Zhao
    • , Mina O. Seedhom
    • , Christelle Harly
    • , Izumi Ohigashi
    • , Michael Kelly
    • , Yousuke Takahama
    • , Jonathan W. Yewdell
    • , Maggie Cam
    •  & Avinash Bhandoola
  • Article
    | Open Access

    Crosstalk between protein oxidation and other post-translational modifications remains unexplored. Here, the authors map the phosphoproteome, cysteine redox proteome and total proteome of adipocytes under acute oxidative stress and reveal crosstalk between cysteine oxidation and phosphorylation-based signalling.

    • Zhiduan Su
    • , James G. Burchfield
    • , Pengyi Yang
    • , Sean J. Humphrey
    • , Guang Yang
    • , Deanne Francis
    • , Sabina Yasmin
    • , Sung-Young Shin
    • , Dougall M. Norris
    • , Alison L. Kearney
    • , Miro A. Astore
    • , Jonathan Scavuzzo
    • , Kelsey H. Fisher-Wellman
    • , Qiao-Ping Wang
    • , Benjamin L. Parker
    • , G. Gregory Neely
    • , Fatemeh Vafaee
    • , Joyce Chiu
    • , Reichelle Yeo
    • , Philip J. Hogg
    • , Daniel J. Fazakerley
    • , Lan K. Nguyen
    • , Serdar Kuyucak
    •  & David E. James
  • Article
    | Open Access

    Inducible genome editing systems often suffer from leakiness or reduced activity. Here the authors develop CRISPR-Switch, a Cre recombinase ON/OFF-controlled sgRNA cassette that allows consecutive editing of two loci.

    • Krzysztof Chylinski
    • , Maria Hubmann
    • , Ruth E. Hanna
    • , Connor Yanchus
    • , Georg Michlits
    • , Esther C. H. Uijttewaal
    • , John Doench
    • , Daniel Schramek
    •  & Ulrich Elling
  • Article
    | Open Access

    How genome stability is maintained at regions of active transcription is currently not entirely clear. Here, the authors reveal an association between base excision repair factors and transcription elongation to modulate DNA repair.

    • Nicola P. Montaldo
    • , Diana L. Bordin
    • , Alessandro Brambilla
    • , Marcel Rösinger
    • , Sarah L. Fordyce Martin
    • , Karine Øian Bjørås
    • , Stefano Bradamante
    • , Per Arne Aas
    • , Antonia Furrer
    • , Lene C. Olsen
    • , Nicolas Kunath
    • , Marit Otterlei
    • , Pål Sætrom
    • , Magnar Bjørås
    • , Leona D. Samson
    •  & Barbara van Loon
  • Article
    | Open Access

    DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. Here the authors present X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA that unveil determinants of LIG1 substrate recognition and enzymatic fidelity.

    • Percy P. Tumbale
    • , Thomas J. Jurkiw
    • , Matthew J. Schellenberg
    • , Amanda A. Riccio
    • , Patrick J O’Brien
    •  & R. Scott Williams
  • Article
    | Open Access

    The neural tissues of coleoids have a greater fraction of nonsynonymous sites than synonymous sites subject to high levels of A-to-I RNA editing, a pattern thought to indicate widespread adaptive editing. Here the authors propose and provide evidence for an alternative, nonadaptive explanation.

    • Daohan Jiang
    •  & Jianzhi Zhang
  • Article
    | Open Access

    In bacteria, the conserved trans-translation system serves as the primary pathway of ribosome rescue, but many species can also use alternative rescue pathways. Here the authors report that in B. subtilis, the rescue factor BrfA binds to non-stop stalled ribosomes, recruits RF2 but not RF1, and induces transition of the ribosome into an open active conformation.

    • Naomi Shimokawa-Chiba
    • , Claudia Müller
    • , Keigo Fujiwara
    • , Bertrand Beckert
    • , Koreaki Ito
    • , Daniel N. Wilson
    •  & Shinobu Chiba
  • Article
    | Open Access

    The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1.

    • Caterina Miro
    • , Emery Di Cicco
    • , Raffaele Ambrosio
    • , Giuseppina Mancino
    • , Daniela Di Girolamo
    • , Annunziata Gaetana Cicatiello
    • , Serena Sagliocchi
    • , Annarita Nappi
    • , Maria Angela De Stefano
    • , Cristina Luongo
    • , Dario Antonini
    • , Feliciano Visconte
    • , Silvia Varricchio
    • , Gennaro Ilardi
    • , Luigi Del Vecchio
    • , Stefania Staibano
    • , Anita Boelen
    • , Cedric Blanpain
    • , Caterina Missero
    • , Domenico Salvatore
    •  & Monica Dentice
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Article
    | Open Access

    ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.

    • Yifeng Zhang
    • , Fabien Thery
    • , Nicholas C. Wu
    • , Emma K. Luhmann
    • , Olivier Dussurget
    • , Mariko Foecke
    • , Clara Bredow
    • , Daniel Jiménez-Fernández
    • , Kevin Leandro
    • , Antje Beling
    • , Klaus-Peter Knobeloch
    • , Francis Impens
    • , Pascale Cossart
    •  & Lilliana Radoshevich
  • Article
    | Open Access

    Pif1 plays multiple roles in maintaining genome stability and preferentially unwinds forked dsDNA. Here the authors solve the structure of Bacteroides sp Pif1 (BaPif1) in complex with a symmetrical double forked dsDNA and provide unprecedented insights into forked dsDNA unwinding by BaPif1.

    • Nannan Su
    • , Alicia K. Byrd
    • , Sakshibeedu R. Bharath
    • , Olivia Yang
    • , Yu Jia
    • , Xuhua Tang
    • , Taekjip Ha
    • , Kevin D. Raney
    •  & Haiwei Song
  • Article
    | Open Access

    In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

    • Koustav Pal
    • , Mattia Forcato
    • , Daniel Jost
    • , Thomas Sexton
    • , Cédric Vaillant
    • , Elisa Salviato
    • , Emilia Maria Cristina Mazza
    • , Enrico Lugli
    • , Giacomo Cavalli
    •  & Francesco Ferrari
  • Article
    | Open Access

    LncRNAs at the HOX gene locus are increased in expression in NPM1 mutant acute myeloid leukemia. In this study, the authors show that one such lncRNA, HOX3B-AS3, has a role in regulating gene transcription and protein synthesis in leukemia cells.

    • Dimitrios Papaioannou
    • , Andreas Petri
    • , Oliver M. Dovey
    • , Sara Terreri
    • , Eric Wang
    • , Frances A. Collins
    • , Lauren A. Woodward
    • , Allison E. Walker
    • , Deedra Nicolet
    • , Felice Pepe
    • , Prasanthi Kumchala
    • , Marius Bill
    • , Christopher J. Walker
    • , Malith Karunasiri
    • , Krzysztof Mrózek
    • , Miranda L. Gardner
    • , Virginia Camilotto
    • , Nina Zitzer
    • , Jonathan L. Cooper
    • , Xiongwei Cai
    • , Xiaoqing Rong-Mullins
    • , Jessica Kohlschmidt
    • , Kellie J. Archer
    • , Michael A. Freitas
    • , Yi Zheng
    • , Robert J. Lee
    • , Iannis Aifantis
    • , George Vassiliou
    • , Guramrit Singh
    • , Sakari Kauppinen
    • , Clara D. Bloomfield
    • , Adrienne M. Dorrance
    •  & Ramiro Garzon