Objective
The fidelity of DNA replication, and therefore the stability of the genome, relies on the DNA Mismatch repair (MMR) pathway, which recognizes DNA replication errors and promotes repair by an excision and re-synthesis mechanism. Mutations that inactivate MMR are associated to Lynch Syndrome, an early-onset cancer disorder characterized by accumulation of mutations at repetitive sequences or microsatellite instability (MSI). Interestingly, a significant number of tumors with MSI have not been correlated with MMR defects, suggesting that additional factors may influence MMR proficiency or DNA replication fidelity
The current proposal aims to investigate alternative molecular mechanisms that result in MMR inactivation and to identify unrecognized genes that are essential for suppression of mutations. We will characterize a subset of Msh6 dominant mutations that abolishes MMR function by inactivating the partially redundant Msh2-Msh3 pathway. Furthermore, we will carry out a genetic screen to identify dominant mutations on the MMR-related genes: MSH3, MLH2 and MLH3 that result in MMR inactivation. Finally, we will carry out a genome-wide screen in budding yeast, to identify mutants that results in increased mutation rates. The human homologs of the identified yeast genes will be further characterized in human cell lines by knock-down experiments and in vivo mutator assays. This proposal is directed to achieve a better understanding of mechanisms preventing accumulation of mutations and will provide relevant information for diagnosis of cancer susceptibility syndromes.
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 genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- 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.
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
See other projects for this call
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
69120 Heidelberg
Germany
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.