Helping Homologues to Find Their Partners DOI: 10.1038/Nrg2154 During Meiotic Prophase, Chromo- Are Sterile

Total Page:16

File Type:pdf, Size:1020Kb

Helping Homologues to Find Their Partners DOI: 10.1038/Nrg2154 During Meiotic Prophase, Chromo- Are Sterile RESEARCH HIGHLIGHTS CHROMOSOME BIOLOGY Helping homologues to find their partners DOI: 10.1038/nrg2154 During meiotic prophase, chromo- are sterile. SUN1 distribution in proteins of the pairing centre local- somes attach to the nuclear envelope wild-type mice varies during the ize. The authors propose a model URLs through their telomeres, facilitating different stages of spermatogenesis, whereby chromosomes run through Entrez homologue pairing. Although the resembling the nuclear envelope a homology check that takes place UNC84A http://www.ncbi.nlm.nih. first description of this chromosome localization of telomeres in primary at SUN-1–ZYG-12 aggregates: gov/sites/entrez?Db=gene&C organization dates back more than a spermatocytes, and fluorescence if they find their partners, synapsis md=ShowDetailView&TermTo Search=77053 century, the molecular mechanisms in situ hybridization (FISH) analy- occurs; otherwise, they keep are still largely unknown. Two sis confirmed that telomeres searching for their homologues. groups now report that, in mice colocalize with SUN1 during mei- In mtf-1/sun-1(jf18) mutants, the and Caenorhabditis elegans, nuclear otic prophase. Telomere attachment homology check is impaired and non- inner membrane proteins have an to the nuclear envelope is impaired homologous synapsis takes place. important role in this process. in Sun1–/– mice, resulting in Altogether, these studies provide Min Han and colleagues showed defective pairing, synapsis and an important addition to our that mice knockout for the nuclear recombination between homologous understanding of the processes of envelope protein SUN1 (also chromosomes. chromosome dynamics during known as UNC84A) develop nor- In a second study, using forward meiosis, which might ultimately mally, but both males and females genetic screening in C. elegans, provide clues about the origins of Verena Jantsch and colleagues meiotic defects that impair human identified a missense mutation in fertility. the matefin gene, mtf-1/sun-1(jf18), Francesca Pentimalli that causes defects in meiotic ORIGINAL RESEARCH PAPERS Ding, X. & chromosome segregation. Using Xu, R. et al. SUN1 is required for telomere FISH, the authors showed that in attachment to nuclear envelope and mutant gonads chromosomes are gametogenesis in mice. Dev. Cell 12, 863–872 (2007) | Penkner, A. et al. The nuclear envelope unable to find their homologous protein Matefin/SUN-1 is required for partners, and instead engage in non- homologous pairing in C. elegans meiosis. homologous synapsis. Furthermore, Dev. Cell 12, 873–885 (2007) FURTHER READING Gerton, J. L. & Hawley, R. S. these mutants fail to form nuclear Homologous chromosome interactions in envelope aggregates of the ZYG-12 meiosis: diversity amidst conservation. Nature protein, which normally form where Rev. Genet. 6, 477–487 (2005) NATURE REVIEWS | GENETICS VOLUME 8 | JULY 2007 © 2007 Nature Publishing Group .
Recommended publications
  • Association Analyses of Known Genetic Variants with Gene
    ASSOCIATION ANALYSES OF KNOWN GENETIC VARIANTS WITH GENE EXPRESSION IN BRAIN by Viktoriya Strumba A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Bioinformatics) in The University of Michigan 2009 Doctoral Committee: Professor Margit Burmeister, Chair Professor Huda Akil Professor Brian D. Athey Assistant Professor Zhaohui S. Qin Research Statistician Thomas Blackwell To Sam and Valentina Dmitriy and Elizabeth ii ACKNOWLEDGEMENTS I would like to thank my advisor Professor Margit Burmeister, who tirelessly guided me though seemingly impassable corridors of graduate work. Throughout my thesis writing period she provided sound advice, encouragement and inspiration. Leading by example, her enthusiasm and dedication have been instrumental in my path to becoming a better scientist. I also would like to thank my co-advisor Tom Blackwell. His careful prodding always kept me on my toes and looking for answers, which taught me the depth of careful statistical analysis. His diligence and dedication have been irreplaceable in most difficult of projects. I also would like to thank my other committee members: Huda Akil, Brian Athey and Steve Qin as well as David States. You did not make it easy for me, but I thank you for believing and not giving up. Huda’s eloquence in every subject matter she explained have been particularly inspiring, while both Huda’s and Brian’s valuable advice made the completion of this dissertation possible. I would also like to thank all the members of the Burmeister lab, both past and present: Sandra Villafuerte, Kristine Ito, Cindy Schoen, Karen Majczenko, Ellen Schmidt, Randi Burns, Gang Su, Nan Xiang and Ana Progovac.
    [Show full text]
  • BMC Cell Biology Biomed Central
    BMC Cell Biology BioMed Central Research article Open Access Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis I-Hsiung Brandon Chen, Michael Huber, Tinglu Guan, Anja Bubeck and Larry Gerace* Address: Department of Cell Biology, The Scripps Research Institute, 10555 N. Torrey Pines Rd., La Jolla CA 92037, USA Email: I-Hsiung Brandon Chen - [email protected]; Michael Huber - [email protected]; Tinglu Guan - [email protected]; Anja Bubeck - [email protected]; Larry Gerace* - [email protected] * Corresponding author Published: 24 October 2006 Received: 01 September 2006 Accepted: 24 October 2006 BMC Cell Biology 2006, 7:38 doi:10.1186/1471-2121-7-38 This article is available from: http://www.biomedcentral.com/1471-2121/7/38 © 2006 Chen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The nuclear lamina is a protein meshwork lining the inner nuclear membrane, which contains a polymer of nuclear lamins associated with transmembrane proteins of the inner nuclear membrane. The lamina is involved in nuclear structure, gene expression, and association of the cytoplasmic cytoskeleton with the nucleus. We previously identified a group of 67 novel putative nuclear envelope transmembrane proteins (NETs) in a large-scale proteomics analysis. Because mutations in lamina proteins have been linked to several human diseases affecting skeletal muscle, we examined NET expression during differentiation of C2C12 myoblasts.
    [Show full text]
  • The Influence of Genetic Variation in Gene Expression
    The Influence of Genetic Variation in Gene Expression Eva King-Fan Chan A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy 2007 School of Biotechnology and Biomolecular Sciences University of New South Wales Certificate of originality I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged. ______________________ Eva Chan 18th July 2007 i Abstract Abstract Variations in gene expression have long been hypothesised to be the major cause of individual differences. An initial focus of this research thesis is to elucidate the genetic regulatory architecture of gene expression. Expression quantitative trait locus (eQTL) mapping analyses have been performed on expression levels of over 22,000 mRNAs from three tissues of a panel of recombinant inbred mice. These analyses are “single-locus” where “linkage” (i.e. significant correlation) between an expression trait and a putative eQTL is considered independently of other loci.
    [Show full text]
  • Snapshot: the Nuclear Envelope II Andrea Rothballer and Ulrike Kutay Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland
    SnapShot: The Nuclear Envelope II Andrea Rothballer and Ulrike Kutay Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland H. sapiens D. melanogaster C. elegans S. pombe S. cerevisiae Cytoplasmic filaments RanBP2 (Nup358) Nup358 CG11856 NPP-9 – – – Nup214 (CAN) DNup214 CG3820 NPP-14 Nup146 SPAC23D3.06c Nup159 Cytoplasmic ring and Nup88 Nup88 (Mbo) CG6819 – Nup82 SPBC13A2.02 Nup82 associated factors GLE1 GLE1 CG14749 – Gle1 SPBC31E1.05 Gle1 hCG1 (NUP2L1, NLP-1) tbd CG18789 – Amo1 SPBC15D4.10c Nup42 (Rip1) Nup98 Nup98 CG10198 Npp-10N Nup189N SPAC1486.05 Nup145N, Nup100, Nup116 Nup 98 complex RAE1 (GLE2) Rae1 CG9862 NPP-17 Rae1 SPBC16A3.05 Gle2 (Nup40) Nup160 Nup160 CG4738 NPP-6 Nup120 SPBC3B9.16c Nup120 Nup133 Nup133 CG6958 NPP-15 Nup132, Nup131 SPAC1805.04, Nup133 SPBP35G2.06c Nup107 Nup107 CG6743 NPP-5 Nup107 SPBC428.01c Nup84 Nup96 Nup96 CG10198 NPP-10C Nup189C SPAC1486.05 Nup145C Outer NPC scaffold Nup85 (PCNT1) Nup75 CG5733 NPP-2 Nup-85 SPBC17G9.04c Nup85 (Nup107-160 complex) Seh1 Nup44A CG8722 NPP-18 Seh1 SPAC15F9.02 Seh1 Sec13 Sec13 CG6773 Npp-20 Sec13 SPBC215.15 Sec13 Nup37 tbd CG11875 – tbd SPAC4F10.18 – Nup43 Nup43 CG7671 C09G9.2 – – – Centrin-21 tbd CG174931, CG318021 R08D7.51 Cdc311 SPCC1682.04 Cdc311 Nup205 tbd CG11943 NPP-3 Nup186 SPCC290.03c Nup192 Nup188 tbd CG8771 – Nup184 SPAP27G11.10c Nup188 Central NPC scaffold Nup155 Nup154 CG4579 NPP-8 tbd SPAC890.06 Nup170, Nup157 (Nup53-93 complex) Nup93 tbd CG7262 NPP-13 Nup97, Npp106 SPCC1620.11, Nic96 SPCC1739.14 Nup53(Nup35, MP44) tbd CG6540 NPP-19 Nup40 SPAC19E9.01c
    [Show full text]
  • Snp Associations with Tuberculosis Susceptibility in a Ugandan
    SNP ASSOCIATIONS WITH TUBERCULOSIS SUSCEPTIBILITY IN A UGANDAN HOUSEHOLD CONTACT STUDY by ALLISON REES BAKER Submitted in partial fulfillment of the requirements For the degree of Master of Science Thesis Advisor: Dr. Catherine M. Stein Department of Epidemiology and Biostatistics CASE WESTERN RESERVE UNIVERSITY August, 2010 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of ______________________________________________________ candidate for the ________________________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Table of Contents...............................................................................................................iii List of Tables ..................................................................................................................... iv Acknowledgements............................................................................................................. v List of Commonly Used Abbreviations ............................................................................. vi Chapter 1: Literature
    [Show full text]
  • Perspectives
    FOCUS ON MECHANOTRANSDUCTION PERSPECTIVES network that can promote coordinated OPINION changes in cell, cytoskeletal and nuclear struc- ture in response to mechanical distortion14 Mechanotransduction at a (FIG. 1a). (Herein, the term hard-wired refers to cytoskeletal structures that are stable enough distance: mechanically coupling the as interconnected units to resist mechanical stresses and thereby maintain shape stabil- ity, even though they undergo continuous extracellular matrix with the nucleus dynamic remodelling at the molecular level.) This model takes into account the observa- Ning Wang, Jessica D. Tytell and Donald E. Ingber tion that individual cytoskeletal filaments can bear significant tensile and compressive loads Abstract | Research in cellular mechanotransduction often focuses on how in living cells because their structural integrity extracellular physical forces are converted into chemical signals at the cell surface. is maintained for longer than the turnover However, mechanical forces that are exerted on surface-adhesion receptors, such time of individual protein monomers15–17. as integrins and cadherins, are also channelled along cytoskeletal filaments and Key to the cellular tensegrity model is concentrated at distant sites in the cytoplasm and nucleus. Here, we explore the the idea that overall cell-shape stability and long-distance force transfer are governed by molecular mechanisms by which forces might act at a distance to induce the level of isometric tension, or ‘prestress’, mechanochemical conversion in the nucleus and alter gene activities. in the cytoskeleton that is generated through the establishment of a force balance between Mechanical forces influence the growth and For example, endothelial cells sense fluid opposing structural elements (that is, micro- shape of virtually every tissue and organ in shear through a cell–cell junctional com- tubules, contractile microfilaments and our bodies.
    [Show full text]
  • The SUN Rises on Meiotic Chromosome Dynamics
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Developmental Cell Review Feature The SUN Rises on Meiotic Chromosome Dynamics Yasushi Hiraoka1,2,* and Abby F. Dernburg3,4,* 1Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita 565-0871, Japan 2Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe 651-2492, Japan 3Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3220, USA 4Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA *Correspondence: [email protected] (Y.H.), [email protected] (A.F.D.) DOI 10.1016/j.devcel.2009.10.014 Recent studies in diverse eukaryotes have implicated a family of nuclear envelope proteins containing SUN domains as key components of meiotic nuclear organization and chromosome dynamics. In many cases, these transmembrane proteins are also known to contribute to centrosome or spindle pole body function in mitotically dividing cells. During meiotic prophase, the apparent role of these SUN-domain proteins, together with their partner KASH-domain proteins, is to connect chromosomes through the intact nuclear envelope to force-generating mechanisms in the cytoplasm. A Family of SUN Proteins In this review, we use these existing names and also refer to these The SUN domain was named for homologous sequences shared genes and their orthologs in mouse and human genomes as Sun4 by Sad1 and UNC-84 proteins (Malone et al., 1999).
    [Show full text]
  • LINC Complexes and Nuclear Positioning [Version 1; Referees: 3
    F1000Research 2019, 8(F1000 Faculty Rev):136 Last updated: 31 JAN 2019 REVIEW Chain reaction: LINC complexes and nuclear positioning [version 1; referees: 3 approved] Brian Burke Institute for Medical Biology, 8A Biomedical Grove, #06-06 Immunos , 138648, Singapore First published: 31 Jan 2019, 8(F1000 Faculty Rev):136 ( Open Peer Review v1 https://doi.org/10.12688/f1000research.16877.1) Latest published: 31 Jan 2019, 8(F1000 Faculty Rev):136 ( https://doi.org/10.12688/f1000research.16877.1) Referee Status: Abstract Invited Referees Nuclear positioning plays an essential role in defining cell architecture and 1 2 3 behaviour in both development and disease, and nuclear location frequently adjusts according to internal and external cues. For instance, during periods of version 1 migration in many cell types, the nucleus may be actively repositioned behind published the microtubule-organising centre. Nuclear movement, for the most part, is 31 Jan 2019 dependent upon coupling of the cytoskeleton to the nuclear periphery. This is accomplished largely through SUN and KASH domain proteins, which together assemble to form LINC (linker of the nucleoskeleton and cytoskeleton) F1000 Faculty Reviews are commissioned complexes spanning the nuclear envelope. SUN proteins of the inner nuclear from members of the prestigious F1000 membrane provide a connection to nuclear structures while acting as a tether Faculty. In order to make these reviews as for outer nuclear membrane KASH proteins. The latter contain binding sites for comprehensive and accessible as possible, diverse cytoskeletal components. Recent publications highlight new aspects of LINC complex regulation revealing that the interplay between SUN and KASH peer review takes place before publication; the partners can strongly influence how the nucleus functionally engages with referees are listed below, but their reports are different branches of the cytoskeleton.
    [Show full text]
  • Nesprin 4 Is an Outer Nuclear Membrane Protein That Can Induce Kinesin-Mediated Cell Polarization
    Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization Kyle J. Rouxa,1,2, Melissa L. Crispa,1, Qian Liua, Daein Kima, Serguei Kozlovb, Colin L. Stewartc, and Brian Burkea,2 aDepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610; cInstitute of Medical Biology, Immunos, 8A Biomedical Grove, Republic of Singapore 138648; and bCenter for Advanced Preclinical Research and Mouse Cancer Genetics Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702 Edited by Don W. Cleveland, University of California at San Diego, La Jolla, CA, and approved December 19, 2008 (received for review September 2, 2008) Nucleocytoplasmic coupling is mediated by outer nuclear mem- by a short luminal sequence. Localization of ONM KASH brane (ONM) nesprin proteins and inner nuclear membrane Sun proteins depends on tethering by SUN domain proteins of the proteins. Interactions spanning the perinuclear space create ne- INM (18). This tethering, involving interactions spanning the sprin–Sun complexes connecting the cytoskeleton to nuclear com- PNS, was originally suggested based on findings that localization ponents. A search for proteins displaying a conserved C-terminal of Anc-1 depends on an INM protein, Unc-84 (19, 20), a sequence present in nesprins 1–3 identified nesprin 4 (Nesp4), a prototype member of the SUN family. new member of this family. Nesp4 is a kinesin-1-binding protein Three mammalian nesprin genes are known [nesprins 1–3 (7)]. that displays Sun-dependent localization to the ONM. Expression For nesprins 1 and 2, the primary transcripts encode a plethora of Nesp4 is associated with dramatic changes in cellular organiza- of alternatively-spliced isoforms (9).
    [Show full text]
  • Francine Blumental De Abreu
    VARIAÇÃO NO NÚMERO DE CÓPIAS GENÔMICAS NA AVALIAÇÃO DE GENES PRINCIPAIS DE PREDISPOSIÇÃO EM PACIENTES COM SÍNDROME DE MAMA-CÓLON TRIADOS PARA MUTAÇÕES NOS GENES BRCA1, BRCA2, TP53, CHEK2, MLH1 E MSH2 FRANCINE BLUMENTAL DE ABREU Tese apresentada à Fundação Antônio Prudente para obtenção do Título de Doutor em Ciências Área de concentração: Oncologia Orientadora: Profª Dra. Silvia Regina Rogatto São Paulo 2012 FICHA CATALOGRÁFICA Preparada pela Biblioteca da Fundação Antônio Prudente Abreu, Francine Blumental de Variação no número de cópias genômicas na avaliação de genes principais de predisposição em pacientes com síndrome de mama- cólon triados para mutações nos genes BRCA1, BRCA2, TP53, CHEK2, MLH1 E MSH2 / Francine Blumental de Abreu – São Paulo, 2012. 245p. Tese (Doutorado)-Fundação Antônio Prudente. Curso de Pós-Graduação em Ciências - Área de concentração: Oncologia. Orientadora: Silvia Regina Rogatto Descritores: 1. SÍNDROME DE LYNCH. 2. NEOPLASIAS DA MAMA. 3. VARIAÇÃO DO NÚMERO DE CÓPIA DO DNA. 4. HIBRIDIZAÇÃO GENÔMICA COMPARATIVA. DEDICATÓRIA A minha família!!!! AGRADECIMENTOS À minha família... Edilucia (II:5) e Antonio (II:6) por serem mais do que pais, por serem mais do que amigos, por serem os meus super heróis! Obrigada pelos abraços, pelas palavras de apoio e de ensinamento, pelo carinho, pelo amor incondicional! Obrigada por estarem sempre disponíveis, por estenderem as mãos depois de uma “rasteira” da vida, por enxugarem as minhas lágrimas! Obrigada principalmente por me fazerem acreditar que momentos difíceis existem,
    [Show full text]
  • Nesprin 4 Is an Outer Nuclear Membrane Protein That Can Induce Kinesin-Mediated Cell Polarization
    Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization Kyle J. Rouxa,1,2, Melissa L. Crispa,1, Qian Liua, Daein Kima, Serguei Kozlovb, Colin L. Stewartc, and Brian Burkea,2 aDepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610; cInstitute of Medical Biology, Immunos, 8A Biomedical Grove, Republic of Singapore 138648; and bCenter for Advanced Preclinical Research and Mouse Cancer Genetics Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702 Edited by Don W. Cleveland, University of California at San Diego, La Jolla, CA, and approved December 19, 2008 (received for review September 2, 2008) Nucleocytoplasmic coupling is mediated by outer nuclear mem- by a short luminal sequence. Localization of ONM KASH brane (ONM) nesprin proteins and inner nuclear membrane Sun proteins depends on tethering by SUN domain proteins of the proteins. Interactions spanning the perinuclear space create ne- INM (18). This tethering, involving interactions spanning the sprin–Sun complexes connecting the cytoskeleton to nuclear com- PNS, was originally suggested based on findings that localization ponents. A search for proteins displaying a conserved C-terminal of Anc-1 depends on an INM protein, Unc-84 (19, 20), a sequence present in nesprins 1–3 identified nesprin 4 (Nesp4), a prototype member of the SUN family. new member of this family. Nesp4 is a kinesin-1-binding protein Three mammalian nesprin genes are known [nesprins 1–3 (7)]. that displays Sun-dependent localization to the ONM. Expression For nesprins 1 and 2, the primary transcripts encode a plethora of Nesp4 is associated with dramatic changes in cellular organiza- of alternatively-spliced isoforms (9).
    [Show full text]
  • Intergenerational Mechanisms of Paternal Stress Transmission
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2018 Intergenerational Mechanisms Of Paternal Stress Transmission Jennifer C. Chan University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Neuroscience and Neurobiology Commons, and the Pharmacology Commons Recommended Citation Chan, Jennifer C., "Intergenerational Mechanisms Of Paternal Stress Transmission" (2018). Publicly Accessible Penn Dissertations. 2790. https://repository.upenn.edu/edissertations/2790 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2790 For more information, please contact [email protected]. Intergenerational Mechanisms Of Paternal Stress Transmission Abstract Evidence that the intergenerational transmission of parental experiences can influence offspring outcomes prompts new consideration for the molecular mechanisms underlying disease risk and resilience. The role of the paternal preconception environment has been of particular interest, stimulating characterization of germ cell epigenetic marks that can respond dynamically to environmental insults and transmit this information at fertilization. Given such exciting potential for sperm epigenetic marks, how these marks are changed by the environment and subsequently impact offspring development are key questions that require investigation. In this dissertation, we address these questions using our established mouse model of paternal stress, where
    [Show full text]