DOCSLIB.ORG

Novel Role for Non-Homologous End Joining in the Formation of Double

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel Role for Non-Homologous End Joining in the Formation of Double Cancer genetics J Med Genet: first published as 10.1136/jmedgenet-2014-102703 on 23 December 2014. Downloaded from ORIGINAL ARTICLE Novel role for non-homologous end joining in the formation of double minutes in methotrexate-resistant colon cancer cells Xiangning Meng,1 Xiuying Qi,1 Huanhuan Guo,1 Mengdi Cai,1 Chunxiang Li,1 Jing Zhu,1 Feng Chen,1 Huan Guo,1 Jie Li,1 Yuzhen Zhao,1 Peng Liu,1 Xueyuan Jia,1 1 1 1 1 1,2 1 Open Access Jingcui Yu, Chunyu Zhang, Wenjing Sun, Yang Yu, Yan Jin, Jing Bai, Scan to access more 3 4 5 1,2 free content Mingrong Wang, Jesusa Rosales, Ki-Young Lee, Songbin Fu ▸ Additional material is ABSTRACT to gene amplification. The Saccharomyces cerevisiae published online only. To view Background Gene amplification is a frequent I-SceI endonuclease system and DSB-inducing agents please visit the journal online (http://dx.doi.org/10.1136/ manifestation of genomic instability that plays a role in have been proven to be crucial in providing jmedgenet-2014-102703). tumour progression and development of drug resistance. support for the role of DSBs in initiating gene amp- 34 1 It is manifested cytogenetically as extrachromosomal lification. In addition, increased frequency of Laboratory of Medical fi Genetics, Harbin Medical double minutes (DMs) or intrachromosomal gene ampli cation in Chinese hamster cells treated University, Harbin, China homogeneously staining regions (HSRs). To better with γ-rays, hypoxia or clastogenic drugs supports a 2Key Laboratory of Medical understand the molecular mechanism by which HSRs correlation between DSBs and gene Genetics (Harbin Medical and DMs are formed and how they relate to the amplification.56 University), Heilongjiang Higher Education Institutions, Harbin, development of methotrexate (MTX) resistance, we used Non-homologous end joining (NHEJ), one of China two model systems of MTX-resistant HT-29 colon cancer the major DSB repair mechanisms, can restore the 3State Key Laboratory of cell lines harbouring amplified DHFR primarily in (i) HSRs original sequence at the break or generate chromo- Molecular Oncology, Cancer and (ii) DMs. somal aberrations7 by ligation of the DNA ends. Institute (Hospital), Peking Results In DM-containing cells, we found increased This process often results in the loss of nucleotides, Union Medical College and 8 Chinese Academy of Medical expression of non-homologous end joining (NHEJ) rendering NHEJ prone to errors. The key proteins Sciences, Beijing, China proteins. Depletion or inhibition of DNA-PKcs, a key involved in NHEJ include DNA-PKcs, KU70 and 4Departments of Biochemistry NHEJ protein, caused decreased DHFR amplification, KU86, among which DNA-PKcs has been shown to and Molecular Biology, disappearance of DMs, increased formation of be the central player. NHEJ-deficient cells are char- University of Calgary, Calgary, Alberta, Canada micronuclei or nuclear buds, which correlated with the acterised by increased sensitivity to DNA-damaging 5Cell Biology & Anatomy, elimination of DHFR, and increased sensitivity to MTX. agents, chromosomal instability, gene amplification Faculty of Medicine, University These findings indicate for the first time that NHEJ plays and predisposition to cancer.6910Previous reports of Calgary, Calgary, Alberta, a specific role in DM formation, and that increased MTX have also shown that cells lacking DNA-PKcs are http://jmg.bmj.com/ Canada sensitivity of DM-containing cells depleted of DNA-PKcs radiosensitive and defective in their ability to repair 11–13 Correspondence to results from DHFR elimination. Conversely, in HSR- DSBs. Conversely, increased level of Dr Songbin Fu, 157 Baojian containing cells, we found no significant change in the DNA-PKcs was observed in adriamycin-resistant Road, Nangang District, Harbin expression of NHEJ proteins. Depletion of DNA-PKcs had cells.14 Adriamycin-resistant cells are known to 150081, China; fusb@ems. no effect on DHFR amplification and resulted in only a exhibit MDR1 amplification, raising the possibility hrbmu.edu.cn, fusongbin@ yahoo.com modest increase in sensitivity to MTX. Interestingly, both that the highly expressed DNA-PKcs may contrib- DM-containing and HSR-containing cells exhibited ute to gene amplification in drug-resistant cells. on September 28, 2021 by guest. Protected copyright. XM, XQ and HG contributed decreased proliferation upon DNA-PKcs depletion. There is evidence that NHEJ is involved in junction equally. Conclusions We demonstrate a novel specific role for formation between amplicon microhomologies NHEJ in the formation of DMs, but not HSRs, in MTX- during gene amplification.15 16 However, the role Received 4 August 2014 Revised 9 October 2014 resistant cells, and that NHEJ may be targeted for the of NHEJ in the formation of DMs and HSRs rela- Accepted 14 October 2014 treatment of MTX-resistant colon cancer. tive to drug resistance in cancer cells remains to be Published Online First investigated. 23 December 2014 Gene dosage depends on factors that regulate INTRODUCTION both gene amplification and gene elimination. The amplification of oncogenes or drug resistance Micronuclei (MNs) are derived from chromosomal genes plays a pivotal role in malignant transform- fragments or whole chromosomes that lag behind ation. Cytogenetic studies have identified two during anaphase and nuclear division.17 Nuclear major topographical structures of amplified DNA buds (NBUDs) are characterised by the same segments: extrachromosomal DNA (double morphology as MNs, with the exception that they minutes, DMs) and intrachromosomal DNA are connected to the nucleus by a stalk of nucleo- (homogeneously staining regions, HSRs).12 plasmic material. Previous studies have shown that However, the underlying molecular mechanism for MNs can be formed via a budding process follow- 18 To cite: Meng X, Qi X, their formation remains unclear. A large body of evi- ing exposure to γ-irradiation. On the other hand, Guo H, et al. J Med Genet dence points to free double-strand DNA breaks amplified DNA can be eliminated by DNA synthe- – 2015;52:135 144. (DSBs) as key intermediates in the process that leads sis inhibitors such as hydroxyurea.19 Meng X, et al. J Med Genet 2015;52:135–144. doi:10.1136/jmedgenet-2014-102703 135 Cancer genetics J Med Genet: first published as 10.1136/jmedgenet-2014-102703 on 23 December 2014. Downloaded from In this study, we used methotrexate (MTX)-resistant HT-29 ZFYVE16: 50-AGGAAGCAACCACCACAAC-30 and 50-CAG human colon cancer cells to study the mechanism involved in the CACCACCAACAGATACA-30,MSH3:50-TGTCTGGTG formation of DMs and HSRs relative to MTX resistance. We TTTCGCCTGAT-30 and 50- TTAGCCAATAACCGCTCTAC-30, show evidence that NHEJ is differentially involved in the forma- CCNH: 50-GTATTGCAGCACTGATTATGTCC-30 and 50-TCATG tion of DMs and HSRs and in the resistance of cancer to MTX. AAAATAGCCATAGGTGA-30,GLRX:50-CCCACATTGTAG GGAATCAT-30 and 50-CCCACAGTCTATTCGTAGCA-30,CAST: METHODS 50-TTGACTCCATAGCCAACCTT-30 and 50-GTCACTTTTCCCA Cell lines and cell culture GAATCCG-30,ACTN:50-ACCGCGAGAAGATGACCCAG-30 and HT-29 colon cancer cells were purchased from the Type Culture 50-TTAATGTCACGCACGATTTAAA-30. Collection of the Chinese Academy of Sciences (Shanghai, China) and were authenticated by the Beijing Microread Western blot analysis Genetics (Beijing, China) using short tandem repeat analysis in Cells were homogenised in lysis buffer supplemented with prote- 2011. DM-containing and HSR-containing cells were generated ase inhibitors and PhosSTOP phosphatase inhibitor (Roche, Basel, by continuous culture of parental HT-29 cells in dulbecco’s Switzerland). Samples were centrifuged at 14 000 rpm for 40 min modified eagle medium DMEM containing high glucose (Gibco at 4°C. The supernatants were resolved by sodium dodecyl sulfate BRL, Gaithersburg, Maryland, USA) and supplemented with polyacrylamide gel electrophoresis (SDS-PAGE), transferred onto MTX (Calbiochem Biochemicals, Darmstadt, Germany). All cell polyvinylidene fluoride (PVDF) membranes (Millipore) and sub- lines were maintained in the presence of 15% fetal calf serum jected to immunoblotting. GAPDH was used for normalisation. (Gibco BRL). The DNA-PK inhibitor, NU7026 (Sigma-Aldrich Co. LLC, Missouri, USA), was added to the medium at a final Immunofluorescence concentration of 10 μM for 5 days. Cells on coverslips were cultured in serum-free medium for 24 h to achieve cell-cycle synchronisation, and then were washed with Antibodies phosphate buffered saline (PBS) and fixed with 4% paraformalde- The antibodies used and their sources are as follows: DHFR hyde for 10 min. Fixed cells were treated with blocking buffer mouse monoclonal antibody was from Abnova, Taipei, Taiwan; (2.5% bovine serum albumin, 0.2 M glycine, 0.1% Triton X-100) KU86 goat polyclonal and DNA-PKcs rabbit polyclonal anti- at 37°C for 30 min, followed by incubation with bodies were from Santa Cruz Biotechnology Inc., Texas, USA; phosphoSer139-H2AX antibody overnight at 4°C. Slides were KU70 mouse monoclonal antibody was from Abcam, then washed with PBS and incubated with the CF488 goat anti- Cambridge, UK; phospho-Ser139 H2AX mouse monoclonal mouse IgG secondary antibody at 37°C for 30 min. Following antibody was from Millipore, Massachusetts, USA; glyceralde- incubation, slides were washed with PBS, and chromosomes were hyde-3-phosphate dehydrogenase (GAPDH) mouse monoclonal counterstained with 40,60-diamidino-2-phenylindole (DAPI). antibody was from Kang Chen Bio-tech, Shanghai, China and Images were obtained using a Leica DM5000B microscope (Leica the CF488 goat
Load more

Recommended publications
  • Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
    Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A.
    [Show full text]
  • High Resolution Physical and Comparative Maps of Horse
    HIGH RESOLUTION PHYSICAL AND COMPARATIVE MAPS OF HORSE CHROMOSOMES 14 (ECA14) AND 21 (ECA21) A Thesis by GLENDA GOH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 2005 Major Subject: Genetics HIGH RESOLUTION PHYSICAL AND COMPARATIVE MAPS OF HORSE CHROMOSOMES 14 (ECA14) AND 21 (ECA21) A Thesis by GLENDA GOH Submitted to Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved as to style and content by: _________________________ _________________________ Bhanu P. Chowdhary Loren C. Skow (Chair of Committee) (Member) _________________________ _________________________ James N. Derr James E. Womack (Member) (Member) _________________________ _________________________ Geoffrey Kapler Evelyn Tiffany-Castiglioni (Chair of Genetics Faculty) (Head of Department) May 2005 Major Subject: Genetics iii ABSTRACT High Resolution Physical and Comparative Maps of Horse Chromosomes 14 (ECA14) and 21 (ECA21). (May 2005) Glenda Goh, B.S. (Hons.), Flinders University of South Australia Chair of Advisory Committee: Dr. Bhanu P. Chowdhary In order to identify genes or markers responsible for economically important traits in the horse, the development of high resolution gene maps of individual equine chromosomes is essential. We herein report the construction of high resolution physically ordered radiation hybrid (RH) and comparative maps for horse chromosomes 14 and 21 (ECA14 and ECA21). These chromosomes predominantly share correspondence with human chromosome 5 (HSA5), though a small region on the proximal part of ECA21 corresponds to a ~5Mb region from the short arm of HSA19. The map for ECA14 consists of 128 markers (83 Type I and 45 Type II) and spans a total of 1828cR.Compared to this, the map of ECA21 is made up of 90 markers (64 Type I and 26 Type II), that segregate into two linkage groups spanning 278 and 760cR each.
    [Show full text]
  • Mai Muudatuntuu Ti on Man Mini
    MAIMUUDATUNTUU US009809854B2 TI ON MAN MINI (12 ) United States Patent ( 10 ) Patent No. : US 9 ,809 ,854 B2 Crow et al. (45 ) Date of Patent : Nov . 7 , 2017 Whitehead et al. (2005 ) Variation in tissue - specific gene expression ( 54 ) BIOMARKERS FOR DISEASE ACTIVITY among natural populations. Genome Biology, 6 :R13 . * AND CLINICAL MANIFESTATIONS Villanueva et al. ( 2011 ) Netting Neutrophils Induce Endothelial SYSTEMIC LUPUS ERYTHEMATOSUS Damage , Infiltrate Tissues, and Expose Immunostimulatory Mol ecules in Systemic Lupus Erythematosus . The Journal of Immunol @(71 ) Applicant: NEW YORK SOCIETY FOR THE ogy , 187 : 538 - 552 . * RUPTURED AND CRIPPLED Bijl et al. (2001 ) Fas expression on peripheral blood lymphocytes in MAINTAINING THE HOSPITAL , systemic lupus erythematosus ( SLE ) : relation to lymphocyte acti vation and disease activity . Lupus, 10 :866 - 872 . * New York , NY (US ) Crow et al . (2003 ) Microarray analysis of gene expression in lupus. Arthritis Research and Therapy , 5 :279 - 287 . * @(72 ) Inventors : Mary K . Crow , New York , NY (US ) ; Baechler et al . ( 2003 ) Interferon - inducible gene expression signa Mikhail Olferiev , Mount Kisco , NY ture in peripheral blood cells of patients with severe lupus . PNAS , (US ) 100 ( 5 ) : 2610 - 2615. * GeneCards database entry for IFIT3 ( obtained from < http : / /www . ( 73 ) Assignee : NEW YORK SOCIETY FOR THE genecards. org /cgi - bin / carddisp .pl ? gene = IFIT3 > on May 26 , 2016 , RUPTURED AND CRIPPLED 15 pages ) . * Navarra et al. (2011 ) Efficacy and safety of belimumab in patients MAINTAINING THE HOSPITAL with active systemic lupus erythematosus : a randomised , placebo FOR SPECIAL SURGERY , New controlled , phase 3 trial . The Lancet , 377 :721 - 731. * York , NY (US ) Abramson et al . ( 1983 ) Arthritis Rheum .
    [Show full text]
  • Prioritizing Parkinson’S Disease Genes Using Population-Scale
    ARTICLE https://doi.org/10.1038/s41467-019-08912-9 OPEN Prioritizing Parkinson’s disease genes using population-scale transcriptomic data Yang I. Li1, Garrett Wong2, Jack Humphrey 3,4 & Towfique Raj2 Genome-wide association studies (GWAS) have identified over 41 susceptibility loci asso- ciated with Parkinson’s Disease (PD) but identifying putative causal genes and the underlying mechanisms remains challenging. Here, we leverage large-scale transcriptomic datasets to 1234567890():,; prioritize genes that are likely to affect PD by using a transcriptome-wide association study (TWAS) approach. Using this approach, we identify 66 gene associations whose predicted expression or splicing levels in dorsolateral prefrontal cortex (DLFPC) and peripheral monocytes are significantly associated with PD risk. We uncover many novel genes associated with PD but also novel mechanisms for known associations such as MAPT, for which we find that variation in exon 3 splicing explains the common genetic association. Genes identified in our analyses belong to the same or related pathways including lysosomal and innate immune function. Overall, our study provides a strong foundation for further mechanistic studies that will elucidate the molecular drivers of PD. 1 Section of Genetic Medicine, Department of Medicine, and Department of Human Genetics, University of Chicago, Chicago 60637 IL, USA. 2 Departments of Neuroscience, and Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, New York 10029 NY, USA. 3 UCL Genetics Institute, Gower Street, London WC1E 6BT, UK. 4 Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1E 6BT, UK. These authors contributed equally: Yang I.
    [Show full text]
  • Rabbit Anti-ZFYVE16/FITC Conjugated Antibody
    SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-ZFYVE16/FITC Conjugated antibody SL19157R-FITC Product Name: Anti-ZFYVE16/FITC Chinese Name: FITC标记的Zinc finger protein结构域ZFYVE16抗体 AI035632; B130024H06Rik; B130031L15; DKFZp686E13162; Endofin; Endosomal associated FYVE domain protein; Endosome associated FYVE domain protein; Endosome-associated FYVE domain protein; KIAA0305; KIAA0305;; mKIAA0305; Alias: OTTMUSP00000029589; RGD1564784; ZFY16_HUMAN; ZFYVE16; Zinc finger FYVE domain containing protein 16; Zinc finger FYVE domain-containing protein 16; Zinc finger, FYVE domain containing 16. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Pig,Cow,Horse,Rabbit,Sheep, ICC=1:50-200IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 88kDa Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLHwww.sunlongbiotech.com conjugated synthetic peptide derived from human ZFYVE16 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of Product Detail: proteins. The encoded protein is thought to regulate membrane trafficking in the endosome.
    [Show full text]
  • Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
    Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo
    [Show full text]
  • NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer
    Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 11-7-2018 Decipher Mechanisms by which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer Jairo Ramos [email protected] Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Clinical Epidemiology Commons Recommended Citation Ramos, Jairo, "Decipher Mechanisms by which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer" (2018). FIU Electronic Theses and Dissertations. 3872. https://digitalcommons.fiu.edu/etd/3872 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida DECIPHER MECHANISMS BY WHICH NUCLEAR RESPIRATORY FACTOR ONE (NRF1) COORDINATES CHANGES IN THE TRANSCRIPTIONAL AND CHROMATIN LANDSCAPE AFFECTING DEVELOPMENT AND PROGRESSION OF INVASIVE BREAST CANCER A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in PUBLIC HEALTH by Jairo Ramos 2018 To: Dean Tomás R. Guilarte Robert Stempel College of Public Health and Social Work This dissertation, Written by Jairo Ramos, and entitled Decipher Mechanisms by Which Nuclear Respiratory Factor One (NRF1) Coordinates Changes in the Transcriptional and Chromatin Landscape Affecting Development and Progression of Invasive Breast Cancer, having been approved in respect to style and intellectual content, is referred to you for judgment.
    [Show full text]
  • Download Special Issue
    BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data BioMed Research International Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data Guest Editors: Julia Tzu-Ya Weng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Copyright © 2014 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “BioMed Research International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Contents Novel Bioinformatics Approaches for Analysis of High-Throughput Biological Data,JuliaTzu-YaWeng, Li-Ching Wu, Wen-Chi Chang, Tzu-Hao Chang, Tatsuya Akutsu, and Tzong-Yi Lee Volume2014,ArticleID814092,3pages Evolution of Network Biomarkers from Early to Late Stage Bladder Cancer Samples,Yung-HaoWong, Cheng-Wei Li, and Bor-Sen Chen Volume 2014, Article ID 159078, 23 pages MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure,Kuei-FangLee, Yi-Cheng Chen, Paul Wei-Che Hsu, Ingrid Y. Liu, and Lawrence Shih-Hsin Wu Volume2014,ArticleID456323,10pages EXIA2: Web Server of Accurate and Rapid Protein Catalytic Residue Prediction, Chih-Hao Lu, Chin-Sheng
    [Show full text]
  • High-Resolution Gene Maps of Horse Chromosomes 14 and 21: Additional Insights Into Evolution and Rearrangements of HSA5 Homologs in Mammals
    Genomics 89 (2007) 89–112 www.elsevier.com/locate/ygeno High-resolution gene maps of horse chromosomes 14 and 21: Additional insights into evolution and rearrangements of HSA5 homologs in mammals Glenda Goh a,1, Terje Raudsepp a,1, Keith Durkin a, Michelle L. Wagner b, Alejandro A. Schäffer c, Richa Agarwala c, Teruaki Tozaki d, ⁎ James R. Mickelson b, Bhanu P. Chowdhary a,e, a Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA b Department of Veterinary Biosciences, University of Minnesota, 295f AS/VM, St. Paul, MN 55108, USA c National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20894, USA d Molecular Genetics Section, Laboratory of Racing Chemistry, Tochigi 320-0851, Japan e Department of Animal Science, College of Agriculture and Life Science, Texas A&M University, College Station, TX 77843, USA Received 12 May 2006; accepted 19 June 2006 Available online 17 August 2006 Abstract High-resolution physically ordered gene maps for equine homologs of human chromosome 5 (HSA5), viz., horse chromosomes 14 and 21 (ECA14 and ECA21), were generated by adding 179 new loci (131 gene-specific and 48 microsatellites) to the existing maps of the two chromosomes. The loci were mapped primarily by genotyping on a 5000-rad horse×hamster radiation hybrid panel, of which 28 were mapped by fluorescence in situ hybridization. The approximately fivefold increase in the number of mapped markers on the two chromosomes improves the average resolution of the map to 1 marker/0.9 Mb.
    [Show full text]
  • Rabbit Anti-TOM1/FITC Conjugated Antibody
    SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-TOM1/FITC Conjugated antibody SL17222R-FITC Product Name: Anti-TOM1/FITC Chinese Name: FITC标记的TOM1蛋白抗体 FLJ33404; OTTHUMP00000028777; Target of myb 1; TOM1_HUMAN； Target of Alias: Myb protein 1; Target of myb1; TOM 1. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Dog,Pig,Cow,Horse,Sheep,Chimpanzee,Rhesus monkey ICC=1:50-200IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 54kDa Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human TOM1 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01Mwww.sunlongbiotech.com TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several Product Detail: alternatively spliced transcript variants encoding different isoforms have been found for this gene.
    [Show full text]
  • Qt8b18n6c6 Nosplash Caf9e24
    Copyright 2014 by Christopher K. Fuller ii For Kai and Lena iii Acknowledgements This work would not have been possible without the support of my research advisor Hao Li. His broad base of interests gave me the freedom to search for something that so well matches my inclinations. I appreciate his insight, enthusiasm, skepticism, and overall encouragement of this effort. I wish to thank my committee, Saunak Sen and Kathleen Giacomini, for their suggestions and support. I wish to thank postdoctoral scholar Xin He for catalyzing the research that became the focus of my work. In addition, I wish to thank postdoctoral scholar Jiashun Zheng for his numerous suggestions and support. I wish to thank the thousands of anonymous individuals who make integrative genomics research possible by providing samples and the researchers dedicated to making these widely available. In addition, I wish to thank the MuTHER and DIAGRAM consortia for providing access to their full summary results. I wish to thank my wife, Sharoni, for her support and for permitting me to encroach on her domain of expertise. You are still the real biologist in the family. Finally, I wish to thank my Mom and Dad ... who took me to the library. iv Abstract Genome-wide association studies (GWAS) have linked various complex diseases to many dozens, sometimes hundreds, of individual genomic loci. Since these are generally of small effect and may lack both functional annotations and an obvious relation to other disease-associated regions, they are difficult to place in a functional context that advances our understanding of the disease.
    [Show full text]
  • C5a Impairs Phagosomal Maturation in the Neutrophil Through Phosphoproteomic Remodeling
    C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodeling Alexander J.T. Wood, … , Klaus Okkenhaug, Andrew Conway Morris JCI Insight. 2020;5(15):e137029. https://doi.org/10.1172/jci.insight.137029. Research Article Immunology Infectious disease Graphical abstract Find the latest version: https://jci.me/137029/pdf RESEARCH ARTICLE C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodeling Alexander J.T. Wood,1 Arlette M. Vassallo,1 Marie-Hélène Ruchaud-Sparagano,2 Jonathan Scott,2 Carmelo Zinnato,1 Carmen Gonzalez-Tejedo,3 Kamal Kishore,3 Clive S. D’Santos,3 A. John Simpson,2,4 David K. Menon,1 Charlotte Summers,1 Edwin R. Chilvers,1,5 Klaus Okkenhaug,6 and Andrew Conway Morris1,6 1Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, United Kingdom. 2Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom. 3Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, United Kingdom. 4Newcastle upon Tyne Hospitals NHS Foundation Trust, Queen Victoria Road, Newcastle upon Tyne, United Kingdom. 5National Heart and Lung Institute, Imperial College, London, United Kingdom. 6Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom. Critical illness is accompanied by the release of large amounts of the anaphylotoxin, C5a. C5a suppresses antimicrobial functions of neutrophils which is associated with adverse outcomes. The signaling pathways that mediate C5a-induced neutrophil dysfunction are incompletely understood. Healthy donor neutrophils exposed to purified C5a demonstrated a prolonged defect (7 hours) in phagocytosis of Staphylococcus aureus. Phosphoproteomic profiling of 2712 phosphoproteins identified persistent C5a signaling and selective impairment of phagosomal protein phosphorylation on exposure to S.
    [Show full text]