Project description
Mechanistic insight into DNA repair
To ensure high-fidelity transmission of genetic information, eukaryotic cells have evolved mechanisms for repairing DNA damage such as double strand-breaks caused by ionising radiation. The homologous recombination pathway is a key DNA repair mechanism that uses the intact chromosome as a template to restore the missing information. The EU-funded DSB Architect project is interested to understand the role of 3D chromosome conformation in this process. Researchers will develop novel technology to characterise the intermolecular and intramolecular interactions and identify key proteins responsible for shaping chromosome conformation.
Objective
The integrity of eukaryotic genomes is constantly challenged by various endogenous and exogenous insults, whereby DNA double-strand breaks (DSBs) are particularly problematic. DSBs can be repaired by multiple pathways, but only the homologous recombination (HR) pathway ensures error-free repair. HR restores missing information around the lesion based on topological interactions with a homologous region on a distinct DNA molecule. HR-directed repair can function across homologous chromosomes in diploid organisms, but is much more efficient between sister chromatids in replicated chromosomes, indicating an important role of chromosome conformation in repair. Sister chromatids are organized by a dynamic interplay between cohesin-mediated loop extrusion, cohesin-mediated sister linkage, and chromatin-based affinity interactions. How these activities shape sister chromatids to support DNA repair is unclear. The proposed project aims to reveal how sister chromatid conformation governs DSB repair efficiency and pathway choice in human cells and to identify and characterize the key molecular factors regulating chromosome conformation for efficient DSB repair. Understanding how intra- and inter-molecular topological interactions contribute to DNA repair will become possible by using a new chromosome conformation capture technology developed in the hosting lab (sister-chromatid sensitive Hi-C). This technology will be combined with a system for acute DSB induction, automated imaging and genomic profiling of DNA repair factors, and targeted protein degradation of cohesin and its regulators to elucidate topological interactions underlying DSB repair. The proposed project will provide insights into how the core machinery shaping the three-dimensional organization of chromosomes contributes to the maintenance of genome integrity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1030 WIEN
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.