Nature Cell Biology contents: August 2013 Volume 15 Number 8, pp 883 - 1017

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Learn more about systems preconfigured precisely for your applications.  bdbiosciences.com/go/screen TABLE OF CONTENTS August 2013 Volume 15, Issue 8 News and Views Research Highlights Articles Letters Corrigenda Erratum Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Combining open-access publishing with a powerful networking platform.  The Frontiers publication process and Research Networking Platform allow you to build your own scientific profiles while following the work of colleagues, mentors and your science heroes.  Connect with your community today    News and Views Top A blooming resolvase at chromosomal fragile sites   pp883 - 885 Achille Pellicioli and Marco Muzi-Falconi doi:10.1038/ncb2812 Common fragile sites (CFSs) are chromosomal regions that are prone to form breaks or gaps during mitosis, in particular following replication stress. The mechanisms modulating CFS expression and promoting safe chromatid transmission to daughter cells are not clear. Now CFS expression is shown to reflect the activity of the MUS81-EME1 resolvase complex which cooperates with the dissolving action of the BLM helicase to prevent uncontrolled chromosome breakage and to promote genome integrity. See also: Letter by Ying et al. | Letter by Naim et al. Linking HSCs to their youth   pp885 - 887 Eric M. Pietras and Emmanuelle Passegué doi:10.1038/ncb2817 Fetal haematopoietic stem cells (HSCs) self-renew extensively to build the blood system from scratch. The protein Lin28b negatively regulates the microRNA let-7 to keep levels of its target Hmga2 high, hence conferring high self-renewal potential to fetal HSCs. This regulatory circuit can be experimentally modulated to boost the lower self-renewal activity of quiescent adult HSCs. See also: Article by Copley et al. Transmitting senescence to the cell neighbourhood   pp887 - 889 Matthew Hoare and Masashi Narita doi:10.1038/ncb2811 Senescence, a cell-autonomous tumour suppressor mechanism, also has pro-tumorigenic effects on neighbouring pre-malignant cells through the senescence-associated secretory phenotype (SASP). The SASP is now shown to be regulated by inflammasomes and to induce paracrine senescence in healthy cells, indicating that senescence may also represent a non-cell-autonomous tumour suppressor mechanism linked to innate immunity. See also: Article by Acosta et al. The multiple talents of kinesin-8   pp889 - 891 Johanna Roostalu and Thomas Surrey doi:10.1038/ncb2820 Multiple activities cooperate to determine the architecture of the mitotic spindle. Kip3 is a kinesin-8 motor protein in budding yeast that acts as a microtubule depolymerase. Now Kip3 is shown to also crosslink and slide antiparallel microtubules, providing additional insights into how kinesin-8 motors control spindle integrity. See also: Article by Su et al. p73 keeps metabolic control in the family   pp891 - 893 Louise Fets and Dimitrios Anastasiou doi:10.1038/ncb2810 The transcription factor p73, a close relative of p53, has complex yet poorly understood roles in tumorigenesis. TAp73, a p73 variant, has now been shown to promote cancer cell proliferation by regulating glucose metabolism to control cellular biosynthetic pathways and antioxidant capacity. See also: Article by Du et al. Cell Biology JOBS of the week Post-doctoral Research Fellow: Cell Biology University of Leeds Postdoctoral fellow in stem cell biology (gene expression and regulation) The University of Texas Medical School At Houston Assistant or Associate Professor in Pluripotent Stem Cell Biology Katholieke Universiteit Leuven postdoctoral position in cell biology Medical University of South Carolina (MUSC) Stem Cell Biology-Post Doctoral Position University of Paris-INSERM More Science jobs from Cell Biology EVENT Stem Cell Biology 24th - 28th September 2013 Cold Spring Harbor, USA More science events from Research Highlights Top Spindle positioning by membrane adjustment | Obesity-associated gut microbiota induce liver cancer | PTEN goes paracrine | Rac1 controls intestinal tumorigenesis Articles Top Role of telomere dysfunction in cardiac failure in Duchenne muscular dystrophy   pp895 - 904 Foteini Mourkioti, Jackie Kustan, Peggy Kraft, John W. Day, Ming-Ming Zhao et al. doi:10.1038/ncb2790 Deficiency in dystrophin leads to death with cardiorespiratory failure in humans, but mice lacking dystrophin have minimal heart defects. Blau and colleagues find that mice that lack dystrophin and have shorter telomeres exhibit cardiac defects similar to human patients, with an increase in oxidative stress. The authors also found that onset of cardiac defects could be delayed by antioxidant treatments and that, strikingly, patients also have shortened telomeres. A tripartite transcription factor network regulates primordial germ cell specification in mice   pp905 - 915 Erna Magnúsdóttir, Sabine Dietmann, Kazuhiro Murakami, Ufuk Günesdogan, Fuchou Tang et al. doi:10.1038/ncb2798 Surani and colleagues use single-cell transcriptomics analysis in a model of mouse primordial germ cell specification to analyse the collaboration between three transcription factors, BLIMP1, PRDM14 and AP2γ, in determining germ cell fate. They find that BLIMP1 binds directly to repress somatic and cell proliferation genes, and at the same time induces AP2γ, which acts together with PRDM14. The three factors are sufficient for specification and form a tripartite interdependent transcriptional network. The Lin28b–let-7–Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells   pp916 - 925 Michael R. Copley, Sonja Babovic, Claudia Benz, David J. H. F. Knapp, Philip A. Beer et al. doi:10.1038/ncb2783 Fetal haematopoietic stem cells (HSCs) display higher self-renewal potential than their adult counterparts. Eaves and colleagues show that adult HSCs express lower levels of Lin28b and higher levels of let-7 miRNA. They demonstrate that Lin28 overexpression, as well as that of Hmga2 (a target of let-7), induces fetal properties in adult HSCs. Conversely, HMGA2 loss in fetal HSCs results in premature induction of adult HSC self-renewal properties. See also: News and Views by Pietras & Passegue Apical domain polarization localizes actin–myosin activity to drive ratchet-like apical constriction   pp926 - 936 Frank M. Mason, Michael Tworoger and Adam C. Martin doi:10.1038/ncb2796 Martin and colleagues analyse the mechanism underlying Twist- and Rho1-driven apical constriction of ventral furrow cells in Drosophila. They characterize the spatial localization of the Rho1 effectors Rok1 and Dia, and their effects on the actomyosin network and adherens junctions. Vesicles modulate an actin network for asymmetric spindle positioning   pp937 - 947 Zuzana Holubcová, Gillian Howard and Melina Schuh doi:10.1038/ncb2802 In mouse oocytes, Rab11a-positive vesicles are associated with actin nucleators. Schuh and colleagues find that these vesicles function as storage reservoirs for actin nucleators, that the actin network can be modulated by altering the number of Rab11a vesicles, and that actin dynamics affect the positioning of the meiotic spindle. Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control   pp948 - 957 Xiaolei Su, Hugo Arellano-Santoyo, Didier Portran, Jeremie Gaillard, Marylin Vantard et al. doi:10.1038/ncb2801 Pellman and colleagues report that the Kip3 kinesin-8 has antiparallel microtubule-sliding activity. The ability of Kip3 to slide antiparallel microtubules, along with its known role in destabilizing microtubules, are important for regulating spindle length. See also: News and Views by Roostalu & Surrey A soft cortex is essential for asymmetric spindle positioning in mouse oocytes   pp958 - 966 Agathe Chaigne, Clément Campillo, Nir S. Gov, Raphaël Voituriez, Jessica Azoury et al. doi:10.1038/ncb2799 Verlhac, Terret and colleagues report that softening of the mouse oocyte cortex during meiosis I is needed for spindle migration and positioning. They show that Mos/mAPK signalling triggers myosin II exclusion from the cortex and an Arp2/3-dependent cortical F-actin thickening that contributes to cortical softening. Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer   pp967 - 977 Georgia Velimezi, Michalis Liontos, Konstantinos Vougas, Theodoros Roumeliotis, Jirina Bartkova et al. doi:10.1038/ncb2795 The ATM checkpoint kinase and the tumour suppressor ARF are thought to act separately to counteract tumorigenesis. Bartek, Gorgoulis and colleagues find that in transformed cells, ATM negatively regulates the levels and activity of ARF. In cell culture and mouse xenograft experiments, ATM inhibition promotes ARF-mediated tumour suppression, demonstrating an interplay between these pathways. A complex secretory program orchestrated by the inflammasome controls paracrine senescence   pp978 - 990 Juan Carlos Acosta, Ana Banito, Torsten Wuestefeld, Athena Georgilis, Peggy Janich et al. doi:10.1038/ncb2784 A property of oncogene-induced senescence (OIS) is the induction of a secretory phenotype, termed the senescence-associated secretome (SASP). Gil and colleagues now provide evidence that senescence can be transmitted in a paracrine manner, by showing that induction of the SASP in cells undergoing OIS by inflammasome-mediated interleukin-1 signalling can promote senescence of normal neighbouring cells. See also: News and Views by Hoare & Narita TAp73 enhances the pentose phosphate pathway and supports cell proliferation   pp991 - 1000 Wenjing Du, Peng Jiang, Anthony Mancuso, Aaron Stonestrom, Michael D. Brewer et al. doi:10.1038/ncb2789 The p53 homologue TAp73 is frequently overexpressed in tumours, suggesting it provides an advantage to cancer cells. Yang and colleagues have investigated the role of TAp73 in tumour cell proliferation and showed that TAp73, but not p53, is a transcriptional activator of glucose-6-phosphate dehydrogenase. Increased expression of this gene promotes the pentose phosphate pathway flux, leading to enhanced biosynthesis and antioxidant defence, both of which have been shown to support optimal cell proliferation and tumour formation. See also: News and Views by Fets & Anastasiou Letters Top MUS81 promotes common fragile site expression   pp1001 - 1007 Songmin Ying, Sheroy Minocherhomji, Kok Lung  Chan, Timea Palmai-Pallag, Wai Kit Chu et al. doi:10.1038/ncb2773 Chromosomal fragile sites (CFSs) are prone to breakage and thus can cause genomic instability. Hickson and colleagues demonstrate that the MUS81 endonuclease localizes to CFSs and mediates their processing, revealing that CFS cleavage is an active process. See also: News and Views by Pellicioli & Muzi-Falconi ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis   pp1008 - 1015 Valeria Naim, Therese Wilhelm, Michelle Debatisse and Filippo Rosselli doi:10.1038/ncb2793 Breakage and rearrangement of common fragile sites (CFSs) can cause genomic instability. Rosselli and colleagues demonstrate that the endonuclease subunit ERCC1 and the endonuclease MUS18–EME1 are recruited to FANCD2-binding CFSs in mitosis to mediate their processing. See also: News and Views by Pellicioli & Muzi-Falconi Corrigenda Top Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment   p1016 Cesar Nombela-Arrieta, Gregory Pivarnik, Beatrice Winkel, Kimberly J. Canty, Brendan Harley et al. doi:10.1038/ncb2813 TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop   p1016 Carmine Settembre, Rossella De Cegli, Gelsomina Mansueto, Pradip K. Saha, Francesco Vetrini et al. doi:10.1038/ncb2814 Erratum Top Emerging regulation and functions of autophagy   p1017 Patricia Boya, Fulvio Reggiori and Patrice Codogno doi:10.1038/ncb2815 Top Advertisement nature.com webcasts Macmillan Science Communication, presents a custom webcast on: Using microfluidics for real-time imaging of in vitro cell models  Register for free and listen on demand  Sponsored by:     Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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