Objective
Numerous DNA repair pathways are required for genomic stability and chromosome maintenance. XPF/ERCC1 protein complex is an evolutionally conserved structure-specific endonuclease involved in nucleotide excision repair (NER) and other DNA repair pathways, making it essential for viability. The pleiotropic phenotypes of XPF/ERCC1 deficiency in humans range from cancer-predisposition to accelerated aging and severe developmental abnormalities. The research outlined here combines biochemical and structural approaches to study XPF/ERCC1 incision 5′ to the lesion during NER. The proposal is guided by the premise that XPA and RPA proteins, two other NER core factors, stimulate XPF/ERCC1 activity. The primary aim is to structurally characterize the multiprotein-DNA assembly in order to elucidate the DNA binding and catalytic activity of XPF/ERCC1. To achieve this we will address how individual DNA binding domains of XPF/ERCC1 contribute to DNA cleavage, how XPA recruits XPF/ERCC1 to sites of NER, and how RPA in conjunction with XPA pre- organize the DNA structure at ds/ss junctions. The public health importance of this research comes from the increasing interest in the regulation of XPF/ERCC1 activity, due to its involvement in DNA repair pathways implicated in the resistance of tumors to chemotherapy. Cancer associated deaths are the number one cause of mortality worldwide and resistance to current chemotherapeutics remains a major clinical hurdle. Sensitizing cancer cells to treatment with DNA damaging chemotherapeutics holds great value. One way to achieve this result is the development of small drug-like molecules targeting DNA binding sites of NER proteins to disrupt the formation of a functional NER complex and decrease its capacity.
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 basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics nucleotides
- 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.
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.
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.
FP7-PEOPLE-2013-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
601 77 Brno
Czechia
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.