Project description
Cohesin in sister chromatid cohesion, DNA damage tolerance, replication and cancer
Cohesin is a highly conserved protein complex that mediates sister chromatid cohesion, repair of double-strand DNA breaks and control of gene transcription by promoting the restart of stalled replication forks. It is also implicated in tumour formation. The details of cohesin’s role in these processes are not known. With the support of the Marie Skłodowska-Curie Actions programme, the RESTART project aims to investigate the interplay between sister chromatid cohesion and DNA damage tolerance, as well as explore their contribution to successful replication and how cohesin mutations cause cancer. This will be explored using a plethora of cutting-edge technologies including yeast genetics, molecular biology, proteomics and bioinformatics.
Objective
Cohesin, an evolutionary conserved ring-shaped protein complex that topologically entraps DNA, has crucial roles in many structural and functional aspects of chromosomes including sister chromatid cohesion, genome organization, gene transcription and DNA repair. The importance of cohesin in the maintenance of genomic stability has been known for some time. Cohesin facilitates double strand breaks repair by homologous recombination and promotes the restart of stalled replication forks by template switching, an error-free DNA tolerance pathway. However, the precise role of cohesin in DNA damage and in the recovery after replication stress is still unknown. Whether cohesin acts exclusively providing close proximity of sister chromatids or its functions exceed simple embracing of DNA has yet to be discerned. Cohesin has been shown to be ubiquitylated upon replication fork arrest. This post-translational modification has been proposed to favour cohesin mobilization and subsequent association with nascent DNA behind the fork. However, the extent to what cohesin dynamics are important in the recovery after replication stress is still to be understood. By a range of multidisciplinary approaches, from biochemistry and enzymology, yeast genetics and molecular biology techniques to high throughput proteomics and bioinformatics analysis of mass spectrometry data, we will gain valuable insight about the interplay between sister chromatid cohesion and DNA damage tolerance and their contribution to successful replication. This basic knowledge about the mechanisms involved in DNA damage responses has demonstrated to be essential in the design of successful strategies against cancer. Remarkably, cohesin is one of the protein complexes most frequently mutated in cancer. This project aims to provide valuable insight about how cohesin mutations cause tumorigenesis.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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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.
37008 SALAMANCA
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.