Transcriptional Silencing Functions of the Yeast Protein Orc1/Sir3 Subfunctionalized After Gene Duplication
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Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
Supplementary Table S5. Differentially Expressed Gene Lists of PD-1High CD39+ CD8 Tils According to 4-1BB Expression Compared to PD-1+ CD39- CD8 Tils
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Immunother Cancer Supplementary Table S5. Differentially expressed gene lists of PD-1high CD39+ CD8 TILs according to 4-1BB expression compared to PD-1+ CD39- CD8 TILs Up- or down- regulated genes in Up- or down- regulated genes Up- or down- regulated genes only PD-1high CD39+ CD8 TILs only in 4-1BBneg PD-1high CD39+ in 4-1BBpos PD-1high CD39+ CD8 compared to PD-1+ CD39- CD8 CD8 TILs compared to PD-1+ TILs compared to PD-1+ CD39- TILs CD39- CD8 TILs CD8 TILs IL7R KLRG1 TNFSF4 ENTPD1 DHRS3 LEF1 ITGA5 MKI67 PZP KLF3 RYR2 SIK1B ANK3 LYST PPP1R3B ETV1 ADAM28 H2AC13 CCR7 GFOD1 RASGRP2 ITGAX MAST4 RAD51AP1 MYO1E CLCF1 NEBL S1PR5 VCL MPP7 MS4A6A PHLDB1 GFPT2 TNF RPL3 SPRY4 VCAM1 B4GALT5 TIPARP TNS3 PDCD1 POLQ AKAP5 IL6ST LY9 PLXND1 PLEKHA1 NEU1 DGKH SPRY2 PLEKHG3 IKZF4 MTX3 PARK7 ATP8B4 SYT11 PTGER4 SORL1 RAB11FIP5 BRCA1 MAP4K3 NCR1 CCR4 S1PR1 PDE8A IFIT2 EPHA4 ARHGEF12 PAICS PELI2 LAT2 GPRASP1 TTN RPLP0 IL4I1 AUTS2 RPS3 CDCA3 NHS LONRF2 CDC42EP3 SLCO3A1 RRM2 ADAMTSL4 INPP5F ARHGAP31 ESCO2 ADRB2 CSF1 WDHD1 GOLIM4 CDK5RAP1 CD69 GLUL HJURP SHC4 GNLY TTC9 HELLS DPP4 IL23A PITPNC1 TOX ARHGEF9 EXO1 SLC4A4 CKAP4 CARMIL3 NHSL2 DZIP3 GINS1 FUT8 UBASH3B CDCA5 PDE7B SOGA1 CDC45 NR3C2 TRIB1 KIF14 TRAF5 LIMS1 PPP1R2C TNFRSF9 KLRC2 POLA1 CD80 ATP10D CDCA8 SETD7 IER2 PATL2 CCDC141 CD84 HSPA6 CYB561 MPHOSPH9 CLSPN KLRC1 PTMS SCML4 ZBTB10 CCL3 CA5B PIP5K1B WNT9A CCNH GEM IL18RAP GGH SARDH B3GNT7 C13orf46 SBF2 IKZF3 ZMAT1 TCF7 NECTIN1 H3C7 FOS PAG1 HECA SLC4A10 SLC35G2 PER1 P2RY1 NFKBIA WDR76 PLAUR KDM1A H1-5 TSHZ2 FAM102B HMMR GPR132 CCRL2 PARP8 A2M ST8SIA1 NUF2 IL5RA RBPMS UBE2T USP53 EEF1A1 PLAC8 LGR6 TMEM123 NEK2 SNAP47 PTGIS SH2B3 P2RY8 S100PBP PLEKHA7 CLNK CRIM1 MGAT5 YBX3 TP53INP1 DTL CFH FEZ1 MYB FRMD4B TSPAN5 STIL ITGA2 GOLGA6L10 MYBL2 AHI1 CAND2 GZMB RBPJ PELI1 HSPA1B KCNK5 GOLGA6L9 TICRR TPRG1 UBE2C AURKA Leem G, et al. -
Congenital Microcephaly
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Sussex Research Online American Journal of Medical Genetics Part C (Seminars in Medical Genetics) ARTICLE Congenital Microcephaly DIANA ALCANTARA AND MARK O'DRISCOLL* The underlying etiologies of genetic congenital microcephaly are complex and multifactorial. Recently, with the exponential growth in the identification and characterization of novel genetic causes of congenital microcephaly, there has been a consolidation and emergence of certain themes concerning underlying pathomechanisms. These include abnormal mitotic microtubule spindle structure, numerical and structural abnormalities of the centrosome, altered cilia function, impaired DNA repair, DNA Damage Response signaling and DNA replication, along with attenuated cell cycle checkpoint proficiency. Many of these processes are highly interconnected. Interestingly, a defect in a gene whose encoded protein has a canonical function in one of these processes can often have multiple impacts at the cellular level involving several of these pathways. Here, we overview the key pathomechanistic themes underlying profound congenital microcephaly, and emphasize their interconnected nature. © 2014 Wiley Periodicals, Inc. KEY WORDS: cell division; mitosis; DNA replication; cilia How to cite this article: Alcantara D, O'Driscoll M. 2014. Congenital microcephaly. Am J Med Genet Part C Semin Med Genet 9999:1–16. INTRODUCTION mid‐gestation although glial cell division formation of the various cortical layers. and consequent brain volume enlarge- Furthermore, differentiating and devel- Congenital microcephaly, an occipital‐ ment does continue after birth [Spalding oping neurons must migrate to their frontal circumference of equal to or less et al., 2005]. Impaired neurogenesis is defined locations to construct the com- than 2–3 standard deviations below the therefore most obviously reflected clini- plex architecture and laminar layered age‐related population mean, denotes cally as congenital microcephaly. -
Diversity of DNA Replication in the Archaea
G C A T T A C G G C A T genes Review Diversity of DNA Replication in the Archaea Darya Ausiannikava * and Thorsten Allers School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-115-823-0304 Academic Editor: Eishi Noguchi Received: 29 November 2016; Accepted: 20 January 2017; Published: 31 January 2017 Abstract: DNA replication is arguably the most fundamental biological process. On account of their shared evolutionary ancestry, the replication machinery found in archaea is similar to that found in eukaryotes. DNA replication is initiated at origins and is highly conserved in eukaryotes, but our limited understanding of archaea has uncovered a wide diversity of replication initiation mechanisms. Archaeal origins are sequence-based, as in bacteria, but are bound by initiator proteins that share homology with the eukaryotic origin recognition complex subunit Orc1 and helicase loader Cdc6). Unlike bacteria, archaea may have multiple origins per chromosome and multiple Orc1/Cdc6 initiator proteins. There is no consensus on how these archaeal origins are recognised—some are bound by a single Orc1/Cdc6 protein while others require a multi- Orc1/Cdc6 complex. Many archaeal genomes consist of multiple parts—the main chromosome plus several megaplasmids—and in polyploid species these parts are present in multiple copies. This poses a challenge to the regulation of DNA replication. However, one archaeal species (Haloferax volcanii) can survive without replication origins; instead, it uses homologous recombination as an alternative mechanism of initiation. This diversity in DNA replication initiation is all the more remarkable for having been discovered in only three groups of archaea where in vivo studies are possible. -
A Novel Motif Governs APC-Dependent Degradation of Drosophila ORC1 in Vivo
Downloaded from genesdev.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press A novel motif governs APC-dependent degradation of Drosophila ORC1 in vivo Marito Araki,1 Hongtao Yu,2 and Maki Asano1,3 1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA; 2Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA Regulated degradation plays a key role in setting the level of many factors that govern cell cycle progression. In Drosophila, the largest subunit of the origin recognition complex protein 1 (ORC1) is degraded at the end of M phase and throughout much of G1 by anaphase-promoting complexes (APC) activated by Fzr/Cdh1. We show here that none of the previously identified APC motifs targets ORC1 for degradation. Instead, a novel sequence, the O-box, is necessary and sufficient to direct Fzr/Cdh1-dependent polyubiquitylation in vitro and degradation in vivo. The O-box is similar to but distinct from the well characterized D-box. Finally, we show that O-box motifs in two other proteins, Drosophila Abnormal Spindle and Schizosaccharomyces pombe Cut2, contribute to Cdh1-dependent polyubiquitylation in vitro, suggesting that the O-box may mediate degradation of a variety of cell cycle factors. [Keywords: APC; cell cycle; ORC1; proteolysis; replication] Received August 5, 2005; revised version accepted August 16, 2005. Progression through the cell cycle relies critically on the and Kirschner 2000), A-box (Littlepage and Ruderman scheduled degradation of an ensemble of proteins. Mis- 2002), and GxEN-box (Castro et al. -
A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinom
Journal of Personalized Medicine Article A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma Szu-Jen Wang 1 and Pei-Ming Yang 2,3,4,5,* 1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung 80249, Taiwan; [email protected] 2 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan 3 Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan 4 Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan 5 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan * Correspondence: [email protected]; Tel.: +886-2-2697-2035 (ext. 143) Abstract: Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi- kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urgently needed. Stathmin 1 (STMN1) is an oncoprotein that destabilizes microtubules and promotes cancer cell migration and invasion. In this study, cancer genomics data mining identified STMN1 as a prognosis biomarker and a therapeutic target for HCC. Co-expressed gene analysis indicated that STMN1 expression was positively associated with cell-cycle-related gene Citation: Wang, S.-J.; Yang, P.-M. A expression. Chemical sensitivity profiling of HCC cell lines suggested that High-STMN1-expressing Bioinformatics Analysis Identifies the HCC cells were the most sensitive to MST-312 (a telomerase inhibitor). -
TERRA Transcription Destabilizes Telomere Integrity to Initiate Break
ARTICLE https://doi.org/10.1038/s41467-021-24097-6 OPEN TERRA transcription destabilizes telomere integrity to initiate break-induced replication in human ALT cells ✉ Bruno Silva 1,4, Rajika Arora 1,3,4, Silvia Bione 2 & Claus M. Azzalin 1 Alternative Lengthening of Telomeres (ALT) is a Break-Induced Replication (BIR)-based mechanism elongating telomeres in a subset of human cancer cells. While the notion that 1234567890():,; spontaneous DNA damage at telomeres is required to initiate ALT, the molecular triggers of this physiological telomere instability are largely unknown. We previously proposed that the telomeric long noncoding RNA TERRA may represent one such trigger; however, given the lack of tools to suppress TERRA transcription in cells, our hypothesis remained speculative. We have developed Transcription Activator-Like Effectors able to rapidly inhibit TERRA transcription from multiple chromosome ends in an ALT cell line. TERRA transcription inhi- bition decreases marks of DNA replication stress and DNA damage at telomeres and impairs ALT activity and telomere length maintenance. We conclude that TERRA transcription actively destabilizes telomere integrity in ALT cells, thereby triggering BIR and promoting telomere elongation. Our data point to TERRA transcription manipulation as a potentially useful target for therapy. 1 Instituto de Medicina Molecular João Lobo Antunes (iMM), Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. 2 Computational Biology Unit, Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, -
(Proper, Insufficient, Aberrant, and NO Reprogramming) Response to the Yamanaka Factors in the Initial Stages of Human I
International Journal of Molecular Sciences Article A PIANO (Proper, Insufficient, Aberrant, and NO Reprogramming) Response to the Yamanaka Factors in the Initial Stages of Human iPSC Reprogramming Kejin Hu Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] Received: 7 April 2020; Accepted: 29 April 2020; Published: 2 May 2020 Abstract: Yamanaka reprogramming is revolutionary but inefficient, slow, and stochastic. The underlying molecular events for these mixed outcomes of induction of pluripotent stem cells (iPSC) reprogramming is still unclear. Previous studies about transcriptional responses to reprogramming overlooked human reprogramming and are compromised by the fact that only a rare population proceeds towards pluripotency, and a significant amount of the collected transcriptional data may not represent the positive reprogramming. We recently developed a concept of reprogramome, which allows one to study the early transcriptional responses to the Yamanaka factors in the perspective of reprogramming legitimacy of a gene response to reprogramming. Using RNA-seq, this study scored 579 genes successfully reprogrammed within 48 h, indicating the potency of the reprogramming factors. This report also tallied 438 genes reprogrammed significantly but insufficiently up to 72 h, indicating a positive drive with some inadequacy of the Yamanaka factors. In addition, 953 member genes within the reprogramome were transcriptionally irresponsive to reprogramming, showing the inability of the reprogramming factors to directly act on these genes. Furthermore, there were 305 genes undergoing six types of aberrant reprogramming: over, wrong, and unwanted upreprogramming or downreprogramming, revealing significant negative impacts of the Yamanaka factors. The mixed findings about the initial transcriptional responses to the reprogramming factors shed new insights into the robustness as well as limitations of the Yamanaka factors. -
The Architecture of the DNA Replication Origin Recognition Complex in Saccharomyces Cerevisiae
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Spiral - Imperial College Digital Repository The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae Zhiqiang Chen, Christian Speck, Patricia Wendel, Chunyan Tang, Bruce Stillman, and Huilin Li ABSTRACT The origin recognition complex (ORC) is conserved in all eukaryotes. The six proteins of the Saccharomyces cerevisiae ORC that form a stable complex bind to origins of DNA replication and recruit prereplicative complex (pre-RC) proteins, one of which is Cdc6. To further understand the function of ORC we recently determined by single-particle reconstruction of electron micrographs a low-resolution, 3D structure of S. cerevisiae ORC and the ORC–Cdc6 complex. In this article, the spatial arrangement of the ORC subunits within the ORC structure is described. In one approach, a maltose binding protein (MBP) was systematically fused to the N or the C termini of the five largest ORC subunits, one subunit at a time, generating 10 MBP-fused ORCs, and the MBP density was localized in the averaged, 2D EM images of the MBP-fused ORC particles. Determining the Orc1–5 structure and comparing it with the native ORC structure localized the Orc6 subunit near Orc2 and Orc3. Finally, subunit–subunit interactions were determined by immunoprecipitation of ORC subunits synthesized in vitro. Based on the derived ORC architecture and existing structures of archaeal Orc1–DNA structures, we propose a model for ORC and suggest how ORC interacts with origin DNA and Cdc6. The studies provide a basis for understanding the overall structure of the pre- RC. -
Cshperspect-REP-A015727 Table3 1..10
Table 3. Nomenclature for proteins and protein complexes in different organisms Mammals Budding yeast Fission yeast Flies Plants Archaea Bacteria Prereplication complex assembly H. sapiens S. cerevisiae S. pombe D. melanogaster A. thaliana S. solfataricus E. coli Hs Sc Sp Dm At Sso Eco ORC ORC ORC ORC ORC [Orc1/Cdc6]-1, 2, 3 DnaA Orc1/p97 Orc1/p104 Orc1/Orp1/p81 Orc1/p103 Orc1a, Orc1b Orc2/p82 Orc2/p71 Orc2/Orp2/p61 Orc2/p69 Orc2 Orc3/p66 Orc3/p72 Orc3/Orp3/p80 Orc3/Lat/p82 Orc3 Orc4/p50 Orc4/p61 Orc4/Orp4/p109 Orc4/p52 Orc4 Orc5L/p50 Orc5/p55 Orc5/Orp5/p52 Orc5/p52 Orc5 Orc6/p28 Orc6/p50 Orc6/Orp6/p31 Orc6/p29 Orc6 Cdc6 Cdc6 Cdc18 Cdc6 Cdc6a, Cdc6b [Orc1/Cdc6]-1, 2, 3 DnaC Cdt1/Rlf-B Tah11/Sid2/Cdt1 Cdt1 Dup/Cdt1 Cdt1a, Cdt1b Whip g MCM helicase MCM helicase MCM helicase MCM helicase MCM helicase Mcm DnaB Mcm2 Mcm2 Mcm2/Nda1/Cdc19 Mcm2 Mcm2 Mcm3 Mcm3 Mcm3 Mcm3 Mcm3 Mcm4 Mcm4/Cdc54 Mcm4/Cdc21 Mcm4/Dpa Mcm4 Mcm5 Mcm5/Cdc46/Bob1 Mcm5/Nda4 Mcm5 Mcm5 Mcm6 Mcm6 Mcm6/Mis5 Mcm6 Mcm6 Mcm7 Mcm7/Cdc47 Mcm7 Mcm7 Mcm7/Prolifera Gmnn/Geminin Geminin Mcm9 Mcm9 Hbo1 Chm/Hat1 Ham1 Ham2 DiaA Ihfa Ihfb Fis SeqA Replication fork assembly Hs Sc Sp Dm At Sso Eco Mcm8 Rec/Mcm8 Mcm8 Mcm10 Mcm10/Dna43 Mcm10/Cdc23 Mcm10 Mcm10 DDK complex DDK complex DDK complex DDK complex Cdc7 Cdc7 Hsk1 l(1)G0148 Hsk1-like 1 Dbf4/Ask Dbf4 Dfp1/Him1/Rad35 Chif/chiffon Drf1 Continued 2 Replication fork assembly (Continued ) Hs Sc Sp Dm At Sso Eco CDK complex CDK complex CDK complex CDK complex CDK complex Cdk1 Cdc28/Cdk1 Cdc2/Cdk1 Cdc2 CdkA Cdk2 Cdc2c CcnA1, A2 CycA CycA1, A2, -
Discovery of a Role for Rab3b in Habituation and Cocaine Induced Locomotor Activation in Mice Using Heterogeneous Functional
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.21.048405; this version posted April 22, 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. 1 2 3 4 Discovery of a role for Rab3b in habituation and cocaine induced 5 locomotor activation in mice using heterogeneous functional genomic analysis 6 7 8 9 Jason A. Bubier1# ,Vivek M. Philip1#, Price E. Dickson1, Guy Mittleman2, Elissa J. Chesler1 10 1The Jackson Laboratory, Bar Harbor, ME 11 2Ball State University, Muncie, IN 12 13 # Equally contributing 1st authors 14 Corresponding Author: 15 Elissa J. Chesler 16 The Jackson Laboratory 17 600 Main Street 18 Bar Harbor ME 04609 19 RUNNING TITLE: Rab3b influences habituation & locomotor response to cocaine 20 KEYWORDS: Genetic, QTL, genomics, cocaine sensitization, habituation 21 22 Guidelines (Max. Limits) 23 Abstract length: 350 words =262 24 Figures and tables: 15 25 Manuscript length: 12000 words 26 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.21.048405; this version posted April 22, 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. 27 Author Contributions: 28 JAB, VMP, GM, EJC Conception or design of the work. JAB, VMP, GM Data collection. 29 JAB, VMP, PED, EJC , Data analysis and interpretation JAB, VMP, PED, EJC Drafting 30 and revising the article. JAB, VMP, PED, GM, EJC Final approval of the version to be 31 published. -
Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms
International Journal of Molecular Sciences Review Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms Megan Schmit and Anja-Katrin Bielinsky * Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] * Correspondence: [email protected] Abstract: Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner. Keywords: Meier-Gorlin syndrome; natural killer cell deficiency; X-linked pigmentary reticulate disorder; Van Esch-O’Driscoll disease; IMAGe syndrome; FILS syndrome; Rothmund-Thomson syndrome; Baller-Gerold syndrome; RAPADILINO Citation: Schmit, M.; Bielinsky, A.-K. Congenital Diseases of DNA Replication: Clinical Phenotypes and 1. Introduction Molecular Mechanisms. Int. J. Mol. 1.1. Replication Initiation Sci.