Objective
Accurate chromosomal DNA replication is of fundamental importance for cellular function, genome integrity and development. In response to replication perturbations, DNA damage response (DDR) and DNA damage tolerance (DDT) pathways become activated and are crucial for detection and tolerance of lesions, as well as for facilitating replication completion and supporting chromosome structural integrity. While important functions and key players of these regulatory processes have been outlined, much less is known about the choreography and mechanistic interplay between DDR and DDT during replication. Moreover, the principles by which they uniquely or commonly affect replication-associated chromosome integrity remain poorly understood.
Here, we will use novel tools and a palette of ingenious genetic, molecular and proteomic based experimental strategies, to investigate the replication stress response triggered by diverse endogenous and exogenous cues, and to identify the underlying mechanisms. We will define the principles of local and temporal regulation of DDT in response to genotoxic stress, with a focus on the mechanisms of SUMO-regulated DNA metabolism processes. Additionally, we will investigate the topological DNA transitions triggered at intrinsically difficult to replicate genomic regions, stalled and terminal forks, with the aim of identifying key mechanisms and regulators of replication integrity at specific complex genomic regions or following specific types of replication stress. Finally, we will explore the relationship between DDT, replication fork architecture and sister chromatid cohesion in the context of DDR- and SUMO-orchestrated DNA transactions. We expect that these studies will reveal new aspects of how replication-associated DNA metabolism processes are inter-related and regulated, uniformly or at specific loci in the genome, and will break new ground in areas of replication mechanisms and chromosome integrity in general.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- 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.1.1. - 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.
20139 Milano
Italy
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.