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Developmental and Genetic Analysis of DNA Double-Strand Break Repair

Ziel

The DNA within our cells is constantly being damaged by both environmental and endogenous agents; of the many forms of DNA damage, the DNA double-strand break (DSB) is considered to be most dangerous. Correct processing of DSBs is not only essential for maintaining genomic integrity but is also required in specific biological processes, such as meiotic recombination and V(D)J recombination, in which DNA breaks are deliberately generated. In animals, defects in the proper response to DSBs can thus have different outcomes: cancer predisposition, embryonic lethality, or compromised immunity. Many genes that play a role in the processing of DSBs have been identified over the past decades, mainly by cloning genes that are responsible for specific human genomic instability or immune deficiency syndromes, and by genetic approaches using unicellular eukaryotes and rodent cell lines. It is, however, evident that many components required in higher eukaryotes are not yet known and the identification of those will be a major challenge for future research. Here, we will for the first time systematically test all genes encoded by an animals genome directly for their involvement in the cellular response to DSB in both somatic and germline tissues: we will use our recently developed transgenic animal models (C. elegans) that visualizes repair of a single localized genomic DNA break in genome wide RNAi screenings to identify (and then characterize) the complement of genes that are required to keep our genome stable, and when mutated can predispose humans to cancer. In parallel, we will study the cellular response to single DNA breaks that are artificially generated during different stages of gametogenesis, as well as address the developmental consequences of DSB induction during the earliest stages of embryonic development – an almost completely unexplored area in the field of genome instability and DNA damage responses.

Wissenschaftliches Gebiet

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Programm/Programme

Thema/Themen

Aufforderung zur Vorschlagseinreichung

ERC-2007-StG
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

ERC-SG - ERC Starting Grant

Gastgebende Einrichtung

ACADEMISCH ZIEKENHUIS LEIDEN
EU-Beitrag
€ 1 022 269,55
Adresse
ALBINUSDREEF 2
2333 ZA Leiden
Niederlande

Auf der Karte ansehen
Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Aktivitätstyp
Higher or Secondary Education Establishments
Kontakt Verwaltung
Liesbeth Dorama (Ms.)
Hauptforscher
Marcel Tijsterman (Dr.)
Links
Gesamtkosten
Keine Daten

Begünstigte (2)

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Letzte Aktualisierung: 16 Juli 2019

Mein Booklet

Permalink: https://cordis.europa.eu/project/id/203379/de

European Union, 2024