Condensin Depletion Causes Genome Decompaction Without Altering the Level of Global Gene Expression in Saccharomyces Cerevisiae
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Dynamic Molecular Linkers of the Genome: the First Decade of SMC Proteins
Downloaded from genesdev.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Dynamic molecular linkers of the genome: the first decade of SMC proteins Ana Losada1 and Tatsuya Hirano2,3 1Spanish National Cancer Center (CNIO), Madrid E-28029, Spain; 2Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA Structural maintenance of chromosomes (SMC) proteins in eukaryotes. The proposed actions of cohesin and con- are chromosomal ATPases, highly conserved from bac- densins offer a plausible, if not complete, explanation for teria to humans, that play fundamental roles in many the sudden appearance of thread-like “substances” (the aspects of higher-order chromosome organization and chromosomes) and their longitudinal splitting during dynamics. In eukaryotes, SMC1 and SMC3 act as the mitosis, first described by Walther Flemming (1882). core of the cohesin complexes that mediate sister chro- Remarkably, SMC proteins are conserved among the matid cohesion, whereas SMC2 and SMC4 function as three phyla of life, indicating that the basic strategy of the core of the condensin complexes that are essential chromosome organization may be evolutionarily con- for chromosome assembly and segregation. Another served from bacteria to humans. An emerging theme is complex containing SMC5 and SMC6 is implicated in that SMC proteins are dynamic molecular linkers of the DNA repair and checkpoint responses. The SMC com- genome that actively fold, tether, and manipulate DNA plexes form unique ring- or V-shaped structures with strands. Their diverse functions range far beyond chro- long coiled-coil arms, and function as ATP-modulated, mosome segregation, and involve nearly all aspects of dynamic molecular linkers of the genome. -
Building the Interphase Nucleus: a Study on the Kinetics of 3D Chromosome Formation, Temporal Relation to Active Transcription, and the Role of Nuclear Rnas
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2020-07-28 Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs Kristin N. Abramo University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Bioinformatics Commons, Cell Biology Commons, Computational Biology Commons, Genomics Commons, Laboratory and Basic Science Research Commons, Molecular Biology Commons, Molecular Genetics Commons, and the Systems Biology Commons Repository Citation Abramo KN. (2020). Building the Interphase Nucleus: A study on the kinetics of 3D chromosome formation, temporal relation to active transcription, and the role of nuclear RNAs. GSBS Dissertations and Theses. https://doi.org/10.13028/a9gd-gw44. Retrieved from https://escholarship.umassmed.edu/ gsbs_diss/1099 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. ABRAMO Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSPOPHY July 28, 2020 Program in Systems Biology, Interdisciplinary Graduate Program BUILDING THE INTERPHASE NUCLEUS: A STUDY ON THE KINETICS OF 3D CHROMOSOME FORMATION, TEMPORAL RELATION TO ACTIVE TRANSCRIPTION, AND THE ROLE OF NUCLEAR RNAS A Dissertation Presented By KRISTIN N. -
Understanding Molecular Functions of the SMC5/6 Complex
G C A T T A C G G C A T genes Review Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex Mariana Diaz 1,2 and Ales Pecinka 1,* ID 1 Institute of Experimental Botany of the Czech Academy of Sciences (IEB), Centre of the Region Haná for Biotechnological and Agricultural Research, Šlechtitelu˚ 31, 77900 Olomouc-Holice, Czech Republic 2 Max Planck Institute for Plant Breeding Research (MPIPZ), Carl-von-Linné-Weg 10, 50829 Cologne, Germany; [email protected] * Correspondence: [email protected]; Tel.: +420-585-238-709 Received: 15 November 2017; Accepted: 4 January 2018; Published: 12 January 2018 Abstract: Chromosome organization, dynamics and stability are required for successful passage through cellular generations and transmission of genetic information to offspring. The key components involved are Structural maintenance of chromosomes (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin complex chromosome condensation and the SMC5/6 complex is specialized in the maintenance of genome stability. Here we summarize recent knowledge on the composition and molecular functions of SMC5/6 complex. SMC5/6 complex was originally identified based on the sensitivity of its mutants to genotoxic stress but there is increasing number of studies demonstrating its roles in the control of DNA replication, sister chromatid resolution and genomic location-dependent promotion or suppression of homologous recombination. Some of these functions appear to be due to a very dynamic interaction with cohesin or other repair complexes. Studies in Arabidopsis indicate that, besides its canonical function in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating plant development, abiotic stress responses, suppression of autoimmune responses and sexual reproduction. -
The Splicing Factor XAB2 Interacts with ERCC1-XPF and XPG for RNA-Loop Processing During Mammalian Development
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.20.211441; this version posted July 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development Evi Goulielmaki1*, Maria Tsekrekou1,2*, Nikos Batsiotos1,2, Mariana Ascensão-Ferreira3, Eleftheria Ledaki1, Kalliopi Stratigi1, Georgia Chatzinikolaou1, Pantelis Topalis1, Theodore Kosteas1, Janine Altmüller4, Jeroen A. Demmers5, Nuno L. Barbosa-Morais3, George A. Garinis1,2* 1. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology- Hellas, GR70013, Heraklion, Crete, Greece, 2. Department of Biology, University of Crete, Heraklion, Crete, Greece, 3. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal, 4. Cologne Center for Genomics (CCG), Institute for Genetics, University of Cologne, 50931, Cologne, Germany, 5. Proteomics Center, Netherlands Proteomics Center, and Department of Biochemistry, Erasmus University Medical Center, the Netherlands. Corresponding author: George A. Garinis ([email protected]) *: equally contributing authors bioRxiv preprint doi: https://doi.org/10.1101/2020.07.20.211441; this version posted July 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. -
FACT Is Recruited to the +1 Nucleosome of Transcribed Genes and Spreads in a Chd1-Dependent Manner
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.20.259960; this version posted August 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner Célia Jeronimo1, Andrew Angel2, Christian Poitras1, Pierre Collin1, Jane Mellor2 and François Robert1,3,4* 1 Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada. 2Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. 3 Département de Médecine, Faculté de Médecine, Université de Montréal, 2900 Boul. Édouard- Montpetit, Montréal, QC H3T 1J4, Canada. 4 Lead Contact *Correspondence: [email protected] The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models for how FACT finds its way to transcriptionally active chromatin include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails and binding partially disassembled nucleosomes. Here, we systematically tested these and other scenarios in Saccharomyces cerevisiae and found that FACT binds transcribed chromatin, not RNAPII. Through a combination of experimental and mathematical modeling evidence, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. -
Transvection in 2012: Site-Specific Transgenes Reveal a Plethora of Trans-Regulatory Effects
COMMENTARY Transvection in 2012: Site-Specific Transgenes Reveal a Plethora of Trans-Regulatory Effects Judith A. Kassis1 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 In this commentary, Judith Kassis discusses Bateman et al., widespread in the Drosophila genome (Bateman et al. 2012; “Comparing Enhancer Action in cis and in trans” and Mellert Mellert and Truman 2012). and Truman “Transvection is Common Throughout the Dro- Both groups of researchers used the phi-C31 system to in- sophila Genome”, which are published in this issue of GENETICS. tegrate transgenes into specific genomic locations to look at the ability of one transgene to activate the expression of another, N Drosophila, homologous chromosomes are paired in so- greatly increasing our knowledge of trans-interactions and sug- Imatic cells (reviewed in McKee 2004), leading to the oppor- gesting many experiments for the future. However, beyond that, tunity for regulatory DNA on one chromosome to influence their approaches to studying transvection and the questions they the expression of a promoter located on the homologous addressed differ. Bateman et al. (2012) used recombination- chromosome (reviewed in Duncan 2002; Kennison and mediated cassette exchange (Bateman et al. 2006) to insert Southworth 2002). Such trans-regulatory interactions were a simple, defined enhancer, the GMR (which consists of five first reported by Ed Lewis (Lewis 1954) who found that binding sites for the eye transcriptional activator Glass) and allelic complementation between particular mutations within adefined promoter driving the expression of either GFP or the bithorax complex did not occur when the pairing of ho- mCherry into three different chromosomal insertion sites to ad- mologous chromosomes was disrupted. -
Nucleolus: a Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky
Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Nucleolus: A Central Hub for Nuclear Functions Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, Sergey Razin, Yegor Vassetzky To cite this version: Olga Iarovaia, Elizaveta Minina, Eugene Sheval, Daria Onichtchouk, Svetlana Dokudovskaya, et al.. Nucleolus: A Central Hub for Nuclear Functions. Trends in Cell Biology, Elsevier, 2019, 29 (8), pp.647-659. 10.1016/j.tcb.2019.04.003. hal-02322927 HAL Id: hal-02322927 https://hal.archives-ouvertes.fr/hal-02322927 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. -
Unit 6-Nucleus
Unit 6-Nucleus Dr. Pallee shree Nucleus • Nucleus is the most important organelle in the cell • It distinguishes eukaryotic from prokaryotic cells • By housing the cell's genome, the nucleus serves both as the repository of genetic information and as the cell's control center • DNA replication, transcription, and RNA processing all take place within the nucleus Cont… • A nucleus is a double-membraned eukaryotic cell organelle that contains the genetic material. • It appears in an oval shape averages 5µm in width. • It often lies in the centre of a cell • The nucleus was the first organelle to be discovered • Nuclei 1st discovered and named by Robert Brown • Role of nucleus 1st demonestrated by Max Hammerling Ultra structure of Nucleus 1. Nuclear envelope 2. nuclear pores 3. Nucleoplasm 4. Nucleolus 5. Chromosomes 1. Structure of Nuclear envelope • The nuclear envelope has a complex structure consisting of a) Two nuclear membranes separated by a perinuclear space measuring about 20–40 nm across b) Underlying nuclear lamina • The nucleus is surrounded by a system of two concentric membranes, called the inner and outer nuclear membranes • The inner and outer nuclear membranes are joined at nuclear pore complexes a. Nuclear membranes • The outer nuclear membrane is continuous with the endoplasmic reticulum, so the space between the • The critical function of the inner and outer nuclear membranes nuclear membranes is to act as is directly connected with the lumen a barrier that separates the of the ER contents of the nucleus from the cytoplasm. • It is functionally similar to the membranes of the ER and has • Like other cell membranes, ribosomes bound to its cytoplasmic each nuclear membrane is a surface but protein composition phospholipid bilayer differ slightly as they are enriched in permeable only to small proteins which binds to cytoskeleton nonpolar molecules • The inner nuclear membrane carries • Other molecules are unable to proteins that are specific to the diffuse through the bilayer. -
What to Do About Those Immunoprecipitation Blues Chip-Seq, DIP-Seq and Related Techniques Are Informative Genome-Wide Assays, but They Don’T Always Work As Planned
technology feature What to do about those immunoprecipitation blues ChIP-seq, DIP-seq and related techniques are informative genome-wide assays, but they don’t always work as planned. Vivien Marx hen the chromatin immunoprecipitation (ChIP) Wor DNA immunoprecipitation (DIP) blues hit, it’s good to realize you’re not alone. ChIP is part of the winding path of characterizing gene function. To find where transcription factors (TFs) or histone marks bind to genomic loci of interest, labs might choose ChIP-seq, which involves cross-linking, then shearing chromatin, immunoprecipitation with an antibody that recognizes a TF or histone mark of interest, followed by sequencing. DIP plus sequencing (DIP-seq) can be used to locate DNA changes such as methylation. ChIP-seq and DIP-seq have been the “cornerstone of epigenetics research” since the field moved from gene-specific epigenetics to the genome- wide approaches of epigenomics, says Colm Nestor, a researcher at Linköping University. Both techniques are cheap, relatively easy to set up, and widely used “because they work very well—when well controlled, that is,” he says. With ChIP-seq, antibodies are sometimes Immunoprecipitation can be used to locate DNA changes such as methylation or places where transcription not as specific as a lab might have first factors bind, and can involve the struggle with artifacts. Credit: A. Lentini, Linköping University assumed1. Some genomic loci can be ‘sticky’ in too many wrong ways, or masked protein epitopes are not ‘sticky’ when they should be. As Dana Farber Cancer Institute researchers differential binding. His former PhD student sharply defined peaks in open chromatin Xiaole Shirley Liu and Clifford Meyer point Dhawal Jain, now a postdoctoral fellow in regions, where nucleosomes are usually out, some of ChIP-seq’s lurking bias issues the lab of Harvard University researcher lacking. -
1 the Nucleoporin ELYS Regulates Nuclear Size by Controlling NPC
bioRxiv preprint doi: https://doi.org/10.1101/510230; this version posted January 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity Predrag Jevtić1,4, Andria C. Schibler2,4, Gianluca Pegoraro3, Tom Misteli2,*, Daniel L. Levy1,* 1 Department of Molecular Biology, University of Wyoming, Laramie, WY, 82071 2 National Cancer Institute, NIH, Bethesda, MD, 20892 3 High Throughput Imaging Facility (HiTIF), National Cancer Institute, NIH, Bethesda, MD, 20892 4 Co-first authors *Corresponding authors: Daniel L. Levy Tom Misteli University of Wyoming National Cancer Institute, NIH Department of Molecular Biology Center for Cancer Research 1000 E. University Avenue 41 Library Drive, Bldg. 41, B610 Laramie, WY, 82071 Bethesda, MD, 20892 Phone: 307-766-4806 Phone: 240-760-6669 Fax: 307-766-5098 Fax: 301-496-4951 E-mail: [email protected] E-mail: [email protected] Running Head: ELYS is a nuclear size effector Abbreviations: NE, nuclear envelope; NPC, nuclear pore complex; ER, endoplasmic reticulum; Nup, nucleoporin; FG-Nup, phenylalanine-glycine repeat nucleoporin 1 bioRxiv preprint doi: https://doi.org/10.1101/510230; this version posted January 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Multi-Scale Organization of the Drosophila Melanogaster Genome
G C A T T A C G G C A T genes Review Multi-Scale Organization of the Drosophila melanogaster Genome Samantha C. Peterson † , Kaylah B. Samuelson † and Stacey L. Hanlon * Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA; [email protected] (S.C.P.); [email protected] (K.B.S.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Interphase chromatin, despite its appearance, is a highly organized framework of loops and bends. Chromosomes are folded into topologically associating domains, or TADs, and each chromosome and its homolog occupy a distinct territory within the nucleus. In Drosophila, genome organization is exceptional because homologous chromosome pairing is in both germline and somatic tissues, which promote interhomolog interactions such as transvection that can affect gene expression in trans. In this review, we focus on what is known about genome organization in Drosophila and discuss it from TADs to territory. We start by examining intrachromosomal organization at the sub-chromosome level into TADs, followed by a comprehensive analysis of the known proteins that play a key role in TAD formation and boundary establishment. We then zoom out to examine interhomolog interactions such as pairing and transvection that are abundant in Drosophila but rare in other model systems. Finally, we discuss chromosome territories that form within the nucleus, resulting in a complete picture of the multi-scale organization of the Drosophila genome. Keywords: Drosophila; topologically associating domain; insulator; pairing; transvection; B chromo- some; cytogenetics Citation: Peterson, S.C.; Samuelson, K.B.; Hanlon, S.L. -
Nature Reviews Molecular Cell Biology
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Sussex Research Online Murray and Carr, Page 1 Smc5/6: a link between DNA-repair and unidirectional replication? Johanne M. Murray and Antony M. Carr* Genome Damage and Stability Centre, University of Sussex, Brighton, Sussex BN1 9RQ, UK. * Corresponding author. [email protected]. Tel +44 (1)1273 678122 Murray and Carr, Page 2 Preface Of the three structural maintenance of chromosome (SMC) complexes, two regulate chromosome dynamics. The third, Smc5/6, functions in homologous recombination and the completion of DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterised target proteins that can dictate their subcellular localization. Smc5/6 functions to establish DNA damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 complex yeast mutants display penetrant phenotypes of rDNA instability. rDNA repeats are replicated unidirectionally. Here we propose that unidirectional replication, combined with global Smc5/6 complex functions can explain the apparent rDNA specificity. Introduction SMC complexes regulate high order chromosome structure. Cohesin maintains the link between replicated sister chromosomes that is essential for equal mitotic segregation. Condensin compacts chromatin prior to mitosis. Smc5/6 complex plays a poorly characterised role in DNA repair. The extensive architectural, structural and sequence similarity between the three SMC complexes suggest common modes of action. There is also an intriguing conservation of domain architecture with bacterial Sbc nucleases and the Mre11-Rad50-Nbs1 (MRN) complex (see Ref.1).