Objective
Telomeres are DNA-protein complexes that reside at the end of the chromosomes. These are key structures in order to prevent loss of genetic information and DNA damage activation at the chromosome termini, thus avoiding genomic instability, which can potentiate tumorigenesis. When a telomere became dysfunctional, for example by loss of telomeric proteins or due to telomere shortening, the DNA damage machinery is activated and the chromosome ends are processed as DNA breaks. This leads to checkpoint activation and repair through chromosome end-joining. Although many have studied how telomere fusions arise in the absence of key telomeric components, the formation of spontaneous end-to-end fusions is still poorly understood. Here we propose to dissect how spontaneous telomere fusions arise. For that we will use as model organism Schizosaccharomyces pombe, which telomeres have great similarities with the mammalian ones. Using a state-of-the-art plasmid assay we will conduct a transposon-based genetic screen in order to unravel new proteins required for the formation of telomeric fusions in a wild-type and unperturbed system. We will then focus on the clearest candidates from the screen and determine their role in telomere biology. Moreover, and in order to further understand how spontaneous telomeric fusions arise, we also aim to investigate the role of telomeric replication in this process. The fact the telomeres are long stretches of repetitive DNA sequences and also due to the formation of secondary structures, replication can be a challenging event, potentiating loss of telomere integrity.
Altogether, we foresee that this project will make a key contribution to our understanding of telomere dysfunction. Importantly, studying how spontaneous fusions arise and finding new components required for end-joining will also give new insights on how a normal cell can become tumorigenic.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics chromosomes
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
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Funding Scheme
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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.
Coordinator
1067-001 LISBOA
Portugal
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.