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  • Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming
    1. Marc Dalod1,2,3,,
    2. Rabie Chelbi1,2,3,
    3. Bernard Malissen1,2,3, and
    4. Toby Lawrence*,1,2,3,
    1. 1Centre d'Immunologie de Marseille‐Luminy (CIML), Aix‐Marseille University UM2, Marseille, France
    2. 2Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, Marseille, France
    3. 3Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France
    1. *Corresponding author. Tel: +33 491269166; Fax: +33 491269430; E‐mail: lawrence{at}ciml.univ-mrs.fr
    1. Senior authors sharing equal contribution.

    Toby Lawrence and colleagues review the characteristics of Dendritic Cell (DC) subsets in the immune system and discuss the complex processes leading to DC functional maturation during steady‐state and inflammatory conditions.

    • dendritic cells
    • homeostasis
    • immunity
    • tolerance
    • Received January 27, 2014.
    • Revision received March 17, 2014.
    • Accepted March 19, 2014.
    Marc Dalod, Rabie Chelbi, Bernard Malissen, Toby Lawrence
  • Coordination of transposon expression with DNA replication in the targeting of telomeric retrotransposons in Drosophila
    1. Liang Zhang1,
    2. Michelle Beaucher1,,
    3. Yan Cheng1, and
    4. Yikang S Rong*,1
    1. 1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute (NCI) NIH, Bethesda, MD, USA
    1. *Corresponding author. Tel: +1 301 451 8335; Fax: +1 301 435 3697; E‐mail: rongy{at}mail.nih.gov
    1. Equal contribution.

    Telomerase‐independent maintenance of Drosophila telomeres via retrotransposon elements involves telomere targeting of ribonucleoprotein structures and coincides with telomere replication, revealing parallels with telomerase‐mediated mechanisms in other species.

    Synopsis

    Telomerase‐independent maintenance of Drosophila telomeres via retrotransposon elements is here shown to involve telomere targeting of ribonucleoprotein structures, in a process that coincides with telomere replication and requires the homolog of a key telomeric protein from telomerase‐dependent species.

    • HeT‐A retrotransposon‐encoded Orf1p protein is produced predominantly in (early) S‐phase cells.

    • Orf1p assembles large, spherical ribonucleoprotein structures (“HeT‐A spheres”) at telomeres.

    • HeT‐A sphere telomere recruitment and telomere replication happen in a similar time window.

    • HeT‐A sphere attachment to telomeres depends on the putative Stn1 homolog Verrocchio.

    • CST complex
    • Drosophila telomere
    • telomere replication
    • telomeric transposon
    • Received September 19, 2013.
    • Revision received March 17, 2014.
    • Accepted March 20, 2014.
    Liang Zhang, Michelle Beaucher, Yan Cheng, Yikang S Rong
  • Crystal structures of the structure‐selective nuclease Mus81‐Eme1 bound to flap DNA substrates
    1. Gwang Hyeon Gwon1,
    2. Aera Jo1,
    3. Kyuwon Baek1,
    4. Kyeong Sik Jin2,
    5. Yaoyao Fu1,
    6. Jong‐Bong Lee3,
    7. YoungChang Kim4 and
    8. Yunje Cho*,1
    1. 1Department of Life Science, Pohang University of Science and Technology, Pohang, South Korea
    2. 2Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, South Korea
    3. 3Department of Physics, Pohang University of Science and Technology, Pohang, South Korea
    4. 4Biosciences Division, Structural Biology Center Argonne National Laboratory, Argonne, IL, USA
    1. *Corresponding author. Tel: +82 54 279 2288; Fax: +82 54 279 8111; E‐mail: yunje{at}postech.ac.kr

    Co‐crystallization of human Mus81‐Eme1 bound to flap DNA substrates reveals key structural features essential for substrate selection and active site positioning during resolution of recombination intermediates.

    Synopsis

    The structure‐selective nuclease Mus81‐Eme1 plays key roles in resolving recombination intermediates such as in the repair of DNA interstrand cross‐links. Co‐crystallization of the human enzyme bound to flap DNA substrates reveals key structural features essential for substrate selection and active site positioning of the incision strand.

    • Mus81‐Eme1 undergoes a structural transition from a closed state to an open state in response to a DNA binding.

    • A specific “5′ end binding pocket” hosts the nicked junction 5′ end of post‐nick duplex DNA.

    • A hydrophobic wedge separates pre‐ and post‐nick duplex and facilitates bending of a nicked substrate.

    • Mus81‐Eme1 shares key structural features with 5′ flap nucleases, but with opposite substrate recognition chirality.

    • crystal structure
    • flap DNA
    • homologous recombination
    • interstrand cross‐link repair
    • Mus81
    • Received January 3, 2014.
    • Revision received March 12, 2014.
    • Accepted March 18, 2014.
    Gwang Hyeon Gwon, Aera Jo, Kyuwon Baek, Kyeong Sik Jin, Yaoyao Fu, Jong‐Bong Lee, YoungChang Kim, Yunje Cho
  • Epigenetic memory: the Lamarckian brain
    1. Andre Fischer*,1,2
    1. 1Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
    2. 2German Center for Neurodegenerative Diseases (DZNE) Goettigen Site, Göttingen, Germany
    1. *Corresponding author. Tel: +49 5513910378; Fax: +49 551399836; E‐mail: afische2{at}gwdg.de

    As part of our review series on Molecular Memory, Andre Fischer discusses epigenetic processes leading to memory formation and transgenerational inheritance under physiological and pathological conditions such as Alzheimer's disease.

    • Alzheimer's disease
    • epigenetics
    • histone‐acetylation
    • memory
    • neurodegeneration
    • non‐coding RNA
    • Received December 10, 2013.
    • Revision received January 9, 2014.
    • Accepted January 13, 2014.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

    Andre Fischer
  • Everything old is new again: (linc)RNAs make proteins!
    1. Stephen M Cohen (scohen{at}imcb.a-star.edu.sg)1,2
    1. 1Institute of Molecular and Cell Biology, Singapore
    2. 2Department of Biological Sciences, National University of Singapore, Singapore

    Long non‐coding RNAs have become the focus of considerable interest over the past few years. Intriguing novel functions have been reported for lincRNAs. Three recent papers identify lincRNAs that work in a more conventional way—encoding protein—in each case a small polypeptide with an interesting biological activity (Magny et al, 2013; Pauli et al, 2014), (Bazzini et al, 2014).

    See also: Magny et al (September 2013),

    Pauli et al and

    Bazzini et al

    Recent advances in ribosome profiling, combined with computational tools and initial functional validations reveal the existence of numerous small peptides that await future functional characterization.

    Stephen M Cohen
  • Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression
    1. Benjamin D Landry1,2,
    2. Claudine E Mapa1,2,
    3. Heather E Arsenault1,2,
    4. Kristin E Poti1,2 and
    5. Jennifer A Benanti*,1,2
    1. 1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA, USA
    2. 2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
    1. *Corresponding author. Tel: +1 508 856 1773; Fax: +1 508 856 4650; E‐mail: Jennifer.Benanti{at}umassmed.edu

    In yeast, Cdk1‐dependent phosphorylation regulates several conserved transcription factors positively and/or negatively, which is important for cell cycle progression and optimal fitness.

    Synopsis

    Cyclin‐dependent kinase Cdk1 controls expression of late cell cycle genes in budding yeast, by positively and negatively regulating several key transcription factors (TFs) through phosphorylation and downstream effects on their stability and/or activity.

    • Cdk1 drives the expression of late cell cycle genes by phosphorylating key transcriptional regulators.

    • Phosphorylation of the repressors Yox1 and Yhp1 promotes their degradation, allowing expression of target genes to peak in M/G1 phase.

    • Cdk1 exerts opposing effects on the activator Hcm1: Phosphorylation both stimulates DNA binding and promotes degradation.

    • Coordinated positive and negative regulation of TFs by Cdk1 is important for cell cycle progression and optimal fitness.

    • Cdk1
    • cell cycle
    • mitosis
    • proteolysis
    • transcription
    • Received September 12, 2013.
    • Revision received March 13, 2014.
    • Accepted March 17, 2014.
    Benjamin D Landry, Claudine E Mapa, Heather E Arsenault, Kristin E Poti, Jennifer A Benanti
  • Miro1: New wheels for transferring mitochondria
    1. Guy Las1,2 and
    2. Orian S Shirihai (shirihai{at}me.com) 1,2
    1. 1Department of Medicine, Boston University School of Medicine, Boston, MA, USA
    2. 2Department of Biochemistry, Faculty of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel

    Mesenchymal stem cells (MSC) are capable of protecting cells harboring mitochondrial damage. This protection is associated with the transfer of mitochondria through tunneling nanotubes (TNT) from MSC to the injured cells. In this issue of The EMBO Journal, the group of Anurag Agrawal shows that mitochondrial transfer is dependent on the levels of Miro1, a mitochondrial Rho‐GTPase that regulates intercellular mitochondrial movement. Miro1 is the first protein shown to accelerate mitochondrial transfer. Amplifying the mitochondrial transfer phenomenon may allow for the study of the mechanisms that regulate it and contribute to our understanding of its role in disease and aging.

    See also: T Ahmad et al

    The mitochondrial Rho‐GTPase Miro1 regulates intercellular mitochondrial transfer between mesenchymal stem cells and epithelial cells in different models of epithelial lung injury.

    Guy Las, Orian S Shirihai