Objective
The genetic information encoded by DNA is under constant attack from both endogenous and exogenous sources of damage. To ensure genome stability and prevent disease, cells use global signaling networks to sense and repair DNA damage. One particularly serious problem is when the replication machinery encounters lesions remaining in the template DNA. In this scenario, cells employ damage bypass mechanisms to complete genome replication and prevent fork breakage. Importantly, these pathways are not restricted to the site of stalling but can also function behind the fork at single-stranded DNA (ssDNA) gaps originated by the re-priming of DNA synthesis downstream of lesions. While it is very well known that ssDNA is the molecular signal that triggers the checkpoint response, it is less clear how and where ssDNA actually arises. Generally, it is assumed to accumulate at stalled replication forks, either by an uncoupling between replicative helicase and polymerase movement or between leading and lagging strand synthesis. However, in a recent study in budding yeast, I found that ssDNA gaps left behind replication forks, and extended by processing factors such as the exonuclease EXO1, constitute the predominant signal that leads to checkpoint activation in response to damaged DNA templates during S phase. Whether this mechanism of checkpoint activation is conserved from yeast to humans remains unexplored. Hence, using a unique set of multidisciplinary approaches, this project aims to address the fundamental question of how DNA damage is sensed during replication in human cells. Interestingly, not only ssDNA gap processing seems important for checkpoint signaling but also for the template switching mechanism of damage bypass. Therefore, this project will also study the function of EXO1 and its association with PCNA at postreplicative ssDNA gaps in order to shed light on the poorly understood mechanism of template switching.
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 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.
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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-EF-ST - Standard EF
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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-2017
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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.
41004 Sevilla
Spain
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.