Ziel
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 tumorigenesis. 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 progressive neurodegenerative disease.
Fully understanding the mechanisms and regulation governing the repair of topoisomerase-induced damage is therefore extremely important to gain new insights into two processes that are a main concern to human health: (a) cancer, both its onset and its therapy, and (b) neurodegenerative disease.
We will combine the use of animal models with biochemistry and molecular and cellular biology techniques to explore different aspects of the repair of topoisomerase-induced breaks. We will mainly focus on our recently identified tyrosyl DNA phosphodiesterase 2 (TDP2), studying its mechanism of action and regulation with special attention to the possible implications in cancer and neurodegeneration.
Wissenschaftliches Gebiet (EuroSciVoc)
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
- NaturwissenschaftenBiowissenschaftenNeurobiologie
- NaturwissenschaftenBiowissenschaftenGenetikDNS
- Medizin- und GesundheitswissenschaftenKlinische MedizinOnkologie
- NaturwissenschaftenBiowissenschaftenGenetikChromosom
- NaturwissenschaftenBiowissenschaftenBiochemieBiomoleküleProteineEnzym
Sie müssen sich anmelden oder registrieren, um diese Funktion zu nutzen
Aufforderung zur Vorschlagseinreichung
FP7-PEOPLE-2010-RG
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
MC-ERG - European Re-integration Grants (ERG)Koordinator
41004 Sevilla
Spanien