Objective
Homologous recombination plays a crucial role to repair DNA strand breaks that may occur spontaneously upon replication fork collapse, during the course of radio- or chemotherapy or in a programmed manner during meiosis. Understanding the molecular mechanisms of re-combinational repair is thus very important not only from a basic research viewpoint, but it is also highly relevant for human health. Here, we will define the function of nucleases in homol-ogous recombination. First, we will study the initial steps in this pathway. We could show previously that the S. cerevisiae Sae2 protein promotes the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex near protein blocked DNA ends. This initiates nucleolytic resection of DNA breaks and activates homologous recombination. Our biochemical setup will be instrumental to define how is the activity of Sae2 regulated by phosphorylation on a mech-anistic level and how physiological protein blocks direct the Mre11 endonuclease. We will ex-tend the study to the human system, and attempt to apply the gained knowledge to improve the efficiency of genome editing by activating recombination in conjunction with the CRISPR-Cas9 nuclease system. Second, we will study how homologous recombination promotes gen-eration of genetic diversity during sexual reproduction. DNA strand breaks are introduced in-tentionally during the prophase of the first meiotic division. They are then processed by the recombination machinery into Holliday junction intermediates. These joint molecules are preferentially converted into crossovers in meiosis, resulting in exchange of genetic infor-mation between the maternal and paternal DNA molecules. This is dependent on the Mlh1-Mlh3 nuclease through a yet unknown mechanism. We will study how Mlh1-Mlh3 in complex with other proteins guarantee crossover outcome to promote diversity of the progeny.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics heredity
- 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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-COG - Consolidator Grant
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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) ERC-2015-CoG
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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.
6500 Bellinzona
Switzerland
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.