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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.

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

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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