Project description
Role of ATR kinase in nuclear mechanoadaptation
In mammalian cells, the ataxia telangiectasia mutated and Rad3-related (ATR) kinase is part of the DNA damage response signalling pathway, involved in maintaining genome integrity by ensuring replication fork stability and coordinating cell cycle progression with DNA repair. ATR is a developmentally essential gene whose mutations have been linked to mental and growth retardation and microcephaly. Recent studies showed that ATR senses mechanical forces and translocates to the nuclear envelope (NE), suggesting an involvement in nuclear mechanoadaptation. The EU-funded MechanoATR project will use molecular biology techniques, imaging technology and the Xenopus laevis model to study the mechanism of ATR recruitment and activation at the NE as well as the physiological relevance of this translocation.
Objective
ATR kinase is involved in maintaining genome integrity by ensuring replication fork stability and coordinating cell cycle progression with the DNA repair. ATR is a developmentally essential gene and in humans and hypomorphic mutations in ATR gene have been linked to Seckel syndrome characterized by mental and growth retardation and microcephaly. While the role of ATR in mediating DNA damage response has been extensively studied, the findings that it senses mechanical forces and translocates to the nuclear envelope (NE), coupled with preliminary data, suggest that this translocation is involved in nuclear mechanoadaptation. However, the mechanism of ATR recruitment and activation at the NE, proteins that are recruited or phosphorylated by ATR and the physiological relevance of ATR in a living organism, remain unknown. We will thus use multidisciplinary approach, advanced molecular biology techniques, cutting edge imaging modalities and the vertebrate model Xenopus Laevis in order to address these questions. Moreover, this proposal aims to identify the downstream consequences of this mechanical force-driven NE-ATR translocation, focusing on nuclear actin dynamics and epigenetic modification of histones.
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 mutation
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences molecular biology
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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.
1678 Nicosia
Cyprus
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.