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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.

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

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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