Project description
Molecular insight into homologous recombination
DNA double-strand breaks (DSBs) emerge from ionising radiation or toxic chemicals and constitute the most dangerous DNA lesions. Homologous recombination is the mechanism by which cells repair DSBs, and it involves the recruitment of the Rad51 recombinase enzyme. The EU-funded SARPBAXZ project aims to study the Rad51 paralogs, cofactors necessary for Rad51 stimulation and efficient DSB repair. Researchers will undertake a multidisciplinary approach to investigate the mechanism by which these auxiliary proteins function. Given that homologous recombination is central for maintaining genomic stability, project results will have important implications for the fields of chromosomal biology and evolution.
Objective
Homologous recombination (HR) is a major mechanism for repairing DNA double-strand breaks (DSBs). A DSB converts one normal chromosome into two pathological chromosomes, making it the severest form of DNA damage. Accordingly, defects in HR lead to genome instability, a potent driver of tumorigenesis. Although Rad51 is the central enzyme involved in HR, several auxiliary factors promote HR by stimulating Rad51. Rad51 paralogs comprise one family of evolutionarily conserved auxiliary factor. Unlike other auxiliary factors, Rad51 paralogs are notorious for their biochemical intractability, a trait that has greatly hindered progress in understanding their function, which in turn has precluded a more complete understanding of HR as a whole. This proposal aims to uncover the molecular mechanisms underlying Rad51 potentiation by Rad51 paralogs. To achieve this, we will employ an interdisciplinary approach combining structural biology, biophysics, biochemistry, and genetics. This proposal is particularly well-placed to deliver novel insights because the historical obstacle in the analysis of Rad51 paralogs—the native purification of functional protein of sufficient yield and quantity—has already been overcome by the Researcher. Furthermore, the Supervisor has extensive expertise in cryo-electron microscopy, which is now a viable approach to visualise the finer structural features of proteins that have been recalcitrant to classical techniques such as X-ray crystallography. Thus, by uniting the experiences of the Researcher and Supervisor, this fellowship has the potential to answer long-standing and significant questions in the field of HR. In addition to maintaining genome stability, HR plays critical roles in gametogenesis, chromosomal biology, and evolution. If awarded, this proposal therefore has the potential to impact several disciplines within the life sciences, and this is especially true given the interdisciplinary nature of the proposed 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
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biophysics
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.3.6. - SOCIETAL CHALLENGES - Europe In A Changing World - Inclusive, Innovative And Reflective Societies
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.
SW7 2AZ London
United Kingdom
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.