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TOPOmics SIGNED

Global dynamics of topoisomerase-induced DNA breaks

Total Cost €

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EC-Contrib. €

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Partnership

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 TOPOmics project word cloud

Explore the words cloud of the TOPOmics project. It provides you a very rough idea of what is the project "TOPOmics" about.

implications    original    cleaving    phosphotyrosyl    integrate    linked    survival    dna    efficacy    anticancer    enzymes    fundamental    nuclear    attached    cellular    picture    tumour    poisons    expression    proteomic    defective    reaction    health    cells    virtually    bond    tumourigenesis    neurological    ligation    enzyme    lesion    consequent    cancer    strand    anomalous    outcomes    dependent    cell    catalysis    molecule    damage    detect    conserved    covalently    intermediates    ends    topoisomerase    human    proliferating    erroneous    nevertheless    topoisomerases    breaks    re    inhibit    therapeutic    rely    final    peculiarity    link    assays    outline    transiently    fulfilling    regulate    chromosome    underlies    screenings    prognostic    resealing    inducing    dynamics    disease    diagnostic    completely    time    persistent    isolate    break    structure    genetic    acquiring    abortive    occurrence    metabolism    compromise    overcome    topology    preferentially    therapy    limitations    genome    subsequently    defects    repair    tools    integrity   

Project "TOPOmics" data sheet

The following table provides information about the project.

Coordinator
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III 

Organization address
address: CALLE MELCHOR FERNANDEZ ALMAGRO 3
city: MADRID
postcode: 28029
website: www.cnio.es

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III ES (MADRID) coordinator 259˙090.00
2    AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS ES (MADRID) participant 1˙740˙909.00

Map

 Project objective

DNA topoisomerases are conserved nuclear enzymes that regulate DNA topology by transiently cleaving and resealing the DNA molecule, fulfilling a fundamental role in virtually every aspect of chromosome metabolism. Nevertheless, erroneous or abortive topoisomerase activity can result in persistent DNA strand breaks with the enzyme covalently attached to 3’ or 5’ DNA ends by a phosphotyrosyl bond, an anomalous structure that can compromise cell survival and/or genome integrity with the consequent implications in tumourigenesis. This peculiarity of topoisomerase catalysis also underlies the anticancer efficacy of topoisomerase poisons, which inhibit the re-ligation step of the reaction inducing the formation of DNA breaks that preferentially target highly proliferating and/or repair defective tumour cells. In addition to this link with cancer therapy, defects in the repair of topoisomerase-induced DNA damage have been linked to neurological disease. Understanding the cellular response to topoisomerase-induced breaks is therefore key for important aspects of human health, with possible implications in the development of novel diagnostic, prognostic and therapeutic tools.

This project aims at acquiring a comprehensive picture of the dynamics of topoisomerase-induced DNA breaks: from their occurrence and repair to the consequences for genome expression and integrity. We rely on the development of completely novel assays to detect and isolate the different intermediates of topoisomerase-induced break repair, and which overcome major traditional limitations in the field. These tools are subsequently used to integrate the time-dependent and genome-wide distribution of the different steps and final outcomes of the process of topoisomerase-induced DNA break repair. Furthermore, we outline original proteomic and genetic screenings to identify novel factors and pathways specifically involved the cellular response to this important type of DNA lesion.

 Publications

year authors and title journal last update
List of publications.
2017 Matthew J. Schellenberg, Jenna Ariel Lieberman, Andrés Herrero-Ruiz, Logan R. Butler, Jason G. Williams, Ana M. Muñoz-Cabello, Geoffrey A. Mueller, Robert E. London, Felipe Cortés-Ledesma, R. Scott Williams
ZATT (ZNF451)–mediated resolution of topoisomerase 2 DNA-protein cross-links
published pages: 1412-1416, ISSN: 0036-8075, DOI: 10.1126/science.aam6468
Science 357/6358 2019-10-14
2017 Weijun Feng, Daisuke Kawauchi, Huiqin Körkel-Qu, Huan Deng, Elisabeth Serger, Laura Sieber, Jenna Ariel Lieberman, Silvia Jimeno-González, Sander Lambo, Bola S. Hanna, Yassin Harim, Malin Jansen, Anna Neuerburg, Olga Friesen, Marc Zuckermann, Vijayanad Rajendran, Jan Gronych, Olivier Ayrault, Andrey Korshunov, David T. W. Jones, Marcel Kool, Paul A. Northcott, Peter Lichter, Felipe Cortés-Ledesma, Stefan M. Pfister, Hai-Kun Liu
Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme
published pages: 14758, ISSN: 2041-1723, DOI: 10.1038/ncomms14758
Nature Communications 8 2019-10-14

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The information about "TOPOMICS" are provided by the European Opendata Portal: CORDIS opendata.

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