Objective
The stalling of DNA replication machinery that occurs as a consequence of encountering unrepaired DNA damage is a challenging problem for cells. In humans, increased error-prone bypass of DNA lesions causes increased mutagenesis, and as a consequence, a rise in the incidence of cancers, whereas error-free replication of damaged DNA contributes to genetic stability. In yeasts, the Rad6-Rad18 ubiquitin-conjugating complex governs three alternative pathways of replication of damaged DNA: the Rad5-dependent err or-free, the DNA polymerase eta dependent error-free, and the polymerase zeta dependent error-prone damage bypass. My research work has contributed to the great progress, which has been made in the past four years toward the understanding the function of translesion synthesis polymerases and unravelling how mutations in polymerase eta cause Xeroderma pigmentosum, a cancer prone syndrome.
However, it is still not known how the Rad5-dependent pathway stimulates error free replication of damaged DN A in yeasts, and whether a similar pathway in humans operates. How protein ubiquitylation governs damage bypass remains to be identified, as well. The goal of my proposed project is to answer these important questions. First, I propose to identify new protein elements in the yeast Rad5-pathway and to reconstitute it in vitro by highly purified protein factors. Second, I plan to examine human HLTF, a recently identified tumour suppressor, which can be the human homologue of yeast Rad5. I further propos e to unravel the role of protein ubiquitylation in giving access to Rad5 and translesion synthesis polymerases to the stalled replication machinery. My study will extend our understanding of the molecular events of DNA damage tolerance pathways, which prevents mutagenesis and carcinogenes.
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
- medical and health sciences clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences molecular biology
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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.
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.
FP6-2004-MOBILITY-12
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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
SZEGED
Hungary
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.