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Molecular Cell
This journal offers authors two options (open access or subscription) to publish research

Aug 17, 2017

Volume 67Issue 4p535-724
Open Archive
On the cover: Bacteria are frequently attacked by phages. Bacteria defend themselves with CRISPR-Cas systems. Phages, in turn, disable bacterial defenses with anti-CRISPRs. In this issue, Pausch et al. (pp. 622–632) describe a variant CRISPR-Cas system that is appears to be resistant to anti-CRISPRs. The cover, an oil painting titled Bacteriophage Attack #1, depicts the potential outcomes of phage attack juxtaposed in a single image. Two different cells (white regions) are attacked by phages. The large cell is protected from the attack—the genome stays intact and the invader remains as an empty shell (translucent phages). The marginalized cell on the right side shows the inverted scenario, in which the bacterial genome is destroyed and the invader reproduces (colored phages). Painting credit: Personal gift from Janis Mengel, University of the Arts Bremen....
On the cover: Bacteria are frequently attacked by phages. Bacteria defend themselves with CRISPR-Cas systems. Phages, in turn, disable bacterial defenses with anti-CRISPRs. In this issue, Pausch et al. (pp. 622–632) describe a variant CRISPR-Cas system that is appears to be resistant to anti-CRISPRs. The cover, an oil painting titled Bacteriophage Attack #1, depicts the potential outcomes of phage attack juxtaposed in a single image. Two different cells (white regions) are attacked by phages. The large cell is protected from the attack—the genome stays intact and the invader remains as an empty shell (translucent phages). The marginalized cell on the right side shows the inverted scenario, in which the bacterial genome is destroyed and the invader reproduces (colored phages). Painting credit: Personal gift from Janis Mengel, University of the Arts Bremen.

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Articles

  • Regulation of hetDNA Length during Mitotic Double-Strand Break Repair in Yeast

    • Xiaoge Guo,
    • Yee Fang Hum,
    • Kevin Lehner,
    • Sue Jinks-Robertson
    Guo et al. examine heteroduplex DNA double-strand break repair products. They find that both 5′ end resection pathways, as well as processive synthesis by Pol δ, are required to generate normal hetDNA profiles. Frequent processing of 3′ ends by Pol δ demonstrates that it is the major extender of both ends.
  • Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation

    • Laure Ferry,
    • Alexandra Fournier,
    • Takeshi Tsusaka,
    • Guillaume Adelmant,
    • Tadahiro Shimazu,
    • Shohei Matano,
    • Olivier Kirsh,
    • Rachel Amouroux,
    • Naoshi Dohmae,
    • Takehiro Suzuki,
    • Guillaume J. Filion,
    • Wen Deng,
    • Maud de Dieuleveult,
    • Lauriane Fritsch,
    • Srikanth Kudithipudi,
    • Albert Jeltsch,
    • Heinrich Leonhardt,
    • Petra Hajkova,
    • Jarrod A. Marto,
    • Kyohei Arita,
    • Yoichi Shinkai,
    • Pierre-Antoine Defossez
    DNA methylation is a key epigenetic mark that must be re-established after each round of replication. Ferry et al. describe a mechanism directly linking DNA methylation maintenance to DNA replication, in which the histone modification machinery acts on a replication protein, allowing recruitment of a key DNA methylation factor.
  • Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation

    • Kyong-Rim Kieffer-Kwon,
    • Keisuke Nimura,
    • Suhas S.P. Rao,
    • Jianliang Xu,
    • Seolkyoung Jung,
    • Aleksandra Pekowska,
    • Marei Dose,
    • Evan Stevens,
    • Ewy Mathe,
    • Peng Dong,
    • Su-Chen Huang,
    • Maria Aurelia Ricci,
    • Laura Baranello,
    • Ying Zheng,
    • Francesco Tomassoni Ardori,
    • Wolfgang Resch,
    • Diana Stavreva,
    • Steevenson Nelson,
    • Michael McAndrew,
    • Adriel Casellas,
    • Elizabeth Finn,
    • Charles Gregory,
    • Brian Glenn St. Hilaire,
    • Steven M. Johnson,
    • Wendy Dubois,
    • Maria Pia Cosma,
    • Eric Batchelor,
    • David Levens,
    • Robert D. Phair,
    • Tom Misteli,
    • Lino Tessarollo,
    • Gordon Hager,
    • Melike Lakadamyali,
    • Zhe Liu,
    • Monique Floer,
    • Hari Shroff,
    • Erez Lieberman Aiden,
    • Rafael Casellas
    In this manuscript, Kieffer-Kwon et al. characterize the epigenetic, remodeling, structural, and architectural changes that affect chromatin as G0 B cells enter the cell cycle upon activation. The data reveal both upstream pathways mediating such processes and their downstream transcriptional impact.
  • Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis

    • Swathi Krishnan,
    • Arne H. Smits,
    • Michiel Vermeulen,
    • Danny Reinberg
    Krishnan et al. discover that chaperone SET evicts phosphorylated linker histones and Shugoshins from mitotic chromosomes. Centromeric Shugoshin and a phosphorylated form of linker histone enriched at the inter-chromatid axis are removed by SET to facilitate sister chromatid resolution. This study illustrates the critical function of SET in safeguarding chromosomal integrity.
  • Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals

    • Yong Xue,
    • Suman K. Pradhan,
    • Fei Sun,
    • Constantinos Chronis,
    • Nancy Tran,
    • Trent Su,
    • Christopher Van,
    • Ajay Vashisht,
    • James Wohlschlegel,
    • Craig L. Peterson,
    • H.T. Marc Timmers,
    • Siavash K. Kurdistani,
    • Michael F. Carey
    Xue et al. show that Mot1, Ino80C, and NC2 (MINC) co-localize on chromatin and coordinate to suppress pervasive transcription in euchromatin and facultative heterochromatin. The function of MINC is conserved from S. cerevisiae to mammals.
  • Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability

    • Amandine Bonnet,
    • Ana R. Grosso,
    • Abdessamad Elkaoutari,
    • Emeline Coleno,
    • Adrien Presle,
    • Sreerama C. Sridhara,
    • Guilhem Janbon,
    • Vincent Géli,
    • Sérgio F. de Almeida,
    • Benoit Palancade
    By combining the genetic manipulation of intron content with genome-wide analyses in both yeasts and human cells, Bonnet et al. reveal a function for introns in counteracting DNA:RNA hybrid (R-loop) formation and its deleterious impact on genetic stability.
  • Structural Variation of Type I-F CRISPR RNA Guided DNA Surveillance

    • Patrick Pausch,
    • Hanna Müller-Esparza,
    • Daniel Gleditzsch,
    • Florian Altegoer,
    • Lennart Randau,
    • Gert Bange
    Pausch et al. report Apo- and target-DNA-bound structures of Cascade type I-Fv. Cas5fv and Cas7fv functionally replace large and small subunits, respectively. Cas5fv facilitates PAM recognition from the DNA major groove site. Type I-Fv lacks the known anti-CRISPR protein target sites and might be resistant to viral Cascade interception.
  • Structural Basis for the Canonical and Non-canonical PAM Recognition by CRISPR-Cpf1

    • Takashi Yamano,
    • Bernd Zetsche,
    • Ryuichiro Ishitani,
    • Feng Zhang,
    • Hiroshi Nishimasu,
    • Osamu Nureki
    Yamano et al. report the crystal structures of L. bacterium Cpf1 bound to the crRNA and its target DNA with distinct PAMs, providing insights into the recognition mechanism of the optimal TTTV and suboptimal C-containing PAMs.
  • Multivalent Recruitment of Human Argonaute by GW182

    • Elad Elkayam,
    • Christopher R. Faehnle,
    • Marjorie Morales,
    • Jingchuan Sun,
    • Huilin Li,
    • Leemor Joshua-Tor
    The interaction between Argonaute and GW182 is essential for miRNA-mediated gene silencing. Here, we show that miRNA binding increases Argonaute’s affinity to GW182 and present the structure of human Argonaute-1 in complex with the hGW182 hook. We also show that GW182 can recruit up to three copies of Argonaute.
  • An Unstable Singularity Underlies Stochastic Phasing of the Circadian Clock in Individual Cyanobacterial Cells

    • Siting Gan,
    • Erin K. O’Shea
    Gan and O’Shea found that environmental signals can elicit stochastic circadian clock phases in individual cyanobacterial cells and quantitatively explained this phenomenon in terms of the dynamical properties of the clock. These properties are physiologically relevant for accurately timed rhythmicity in changing environmental conditions.
  • Activation of the Unfolded Protein Response by Lipid Bilayer Stress

    • Kristina Halbleib,
    • Kristina Pesek,
    • Roberto Covino,
    • Harald F. Hofbauer,
    • Dorith Wunnicke,
    • Inga Hänelt,
    • Gerhard Hummer,
    • Robert Ernst
    The unfolded protein response (UPR) controls the secretory capacity of a cell and is activated by accumulating unfolded proteins in the lumen of the ER. More recently, it became obvious that aberrant membrane lipid compositions of the ER are equally potent in activating the UPR. Halbleib et al. identify a membrane-based mechanism of UPR activation and establish that Ire1, the most conserved transducer of ER stress, uses an amphipathic helix to sense and respond to aberrant physical properties of the ER membrane.
  • Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport

    • Arvindhan Nagarajan,
    • Shaillay Kumar Dogra,
    • Lisha Sun,
    • Neeru Gandotra,
    • Thuy Ho,
    • Guoping Cai,
    • Gary Cline,
    • Priti Kumar,
    • Robert A. Cowles,
    • Narendra Wajapeyee
    Nagarajan et al. show that PON2 is overexpressed in pancreatic cancer and is necessary for pancreatic cancer growth and metastasis. PON2 increases glucose uptake to protect pancreatic cancer cells from detachment-induced cell death, which, in part, occurs through suppression of AMPK→FOXO3A→PUMA signaling pathway.

Short Article

  • Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants

    • Jiliang Hu,
    • Huanjie Yang,
    • Jinye Mu,
    • Tiancong Lu,
    • Juli Peng,
    • Xian Deng,
    • Zhaosheng Kong,
    • Shilai Bao,
    • Xiaofeng Cao,
    • Jianru Zuo
    Hu et al. report that nitric oxide positively regulates the methyltransferase activity of Arabidopsis PRMT5 through S-nitrosylation at Cys-125 during stress responses. S-nitrosylation at Cys-125 enhances the level of Arg symmetric dimethylation, leading to proper splicing-specific pre-mRNA of stress-related genes and eventually boosting the tolerance to stresses.

Resource

  • Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening

    • Daniela M. Arduino,
    • Jennifer Wettmarshausen,
    • Horia Vais,
    • Paloma Navas-Navarro,
    • Yiming Cheng,
    • Anja Leimpek,
    • Zhongming Ma,
    • Alba Delrio-Lorenzo,
    • Andrea Giordano,
    • Cecilia Garcia-Perez,
    • Guillaume Médard,
    • Bernhard Kuster,
    • Javier García-Sancho,
    • Dejana Mokranjac,
    • J. Kevin Foskett,
    • M. Teresa Alonso,
    • Fabiana Perocchi
    Arduino et al. develop a high-throughput drug discovery strategy to identify chemical modulators of the mitochondrial calcium uniporter. They find that mitoxantrone is a selective and direct inhibitor of the MCU channel.
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