Objective
Our genetic material is continually subjected to damage and efficient repair is needed for cancer avoidance. DNA double-strand breaks are cytotoxic and are repaired either by Non Homologous End-Joining or Homologous Recombination (HR). HR provides an important function in DNA repair, where it serves the dual purpose of mending broken chromosomes and recovering sequence information that might be lost at sites of DNA breaks. The recombination process is initiated by exchange of strands between two homologous DNA duplexes (in mitotic cells, recombination generally occurs between two sister chromatids) and the resulting joint molecules can mature into four-way structures known as Holliday junctions. Similar DNA intermediates can be generated during DNA replication via regression of stalled replication forks, which may create a requirement for HJ resolution/dissolution during replication. The primary mechanism of HJ processing involves the BTRR complex which ‘dissolves’ HJs to form non-crossovers, a reaction that is critical to avoid loss of heterozygosity and tumourigenesis. HJs that persist to the late stages of the cell cycle are resolved by the structure-specific endonucleases MUS81-EME1, SLX1-SLX4 or GEN1. Our goal is to address the mechanism of action of the BTRR complex during dHJ dissolution. Understanding this process will further our knowledge of the cancer predisposition disease Bloom’s Syndrome, and will expand our understanding of the relationships between defects in recombinational repair and tumourigenesis.
To gain insight into the mechanism of HJ processing by the BTRR complex we will:
1. Determine the molecular mechanism of HJ dissolution using structural and biochemical approaches.
2. Define the interaction surfaces between components of the BTRR complex and how these interactions contribute to the HJ dissolution.
3. Determine the importance of BLM/BTRR dimer formation for in vivo functionality and correlate with mutations found in BS patients.
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 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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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IEF
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Funding Scheme
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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.
Coordinator
NW1 1AT London
United Kingdom
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