Objective
Challenges to the stable maintenance of the human genome can come from both endogenous and exogenous
sources. However, one of the major threats to genome stability occurs during normal DNA metabolism. The
genome is particularly susceptible to perturbation during the S-phase of the cell cycle when DNA replication
occurs. This is because DNA replication forks can encounter chemical adducts, DNA secondary structures,
topological constraints or bound proteins that hinder their progression. In actively proliferating cells, such as
stem cells, replication perturbation can lead to fork stalling, breakage or collapse. These scenarios can, in
turn, generate deleterious chromosomal rearrangements that have the potential to initiate human disease.
Despite recent advances in our understanding of the biochemical process of DNA replication, the precise
details of the events occurring at sites where replication forks have been perturbed remain poorly
characterised. This is because in-depth analysis of the perturbation of replication represents a major technical
challenge, principally because adducts and lesions generated by DNA damaging agents are randomly
distributed throughout the genome at sites that cannot be controlled or predicted. To overcome this technical
limitation, we have developed systems for site-specific perturbation of DNA replication that can be
transferred to any locus in any cell type. The aim is to define how replication fork perturbation is detected
and engaged by cellular stress-response factors, and then tolerated or repaired. This highly integrated
proposal, and the pioneering technologies that will be used to fulfil our ambitious aims, will have significant
implications for the understanding not only of replication perturbation and its effects on chromosome
dynamics in mitosis, but also of the role of replication stress in the aetiology of cancer and premature ageing.
It will open up new horizons both in and across these fields of research.
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
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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.
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.
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.
ERC-2012-ADG_20120314
See other projects for this call
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.
Host institution
1165 KOBENHAVN
Denmark
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.