Objective
Although a number of risk factors associated with cancer have been well established for many years, there is an emerging need for delineation of the role of DNA repair factors relative to cancer risk, and especially the discovery and quantification of risks associated with gene mutations in double strand break (DSB) repair factors (e.g. BRCA1, DNA-PK, Lig4, XRCC4). In addition, higher levels of oxidative stress (reactive oxygen species, ROS), DNA damage and/or defective DNA repair have been reported in different malignancies and tumors. The long term objective of this project is to identify the role(s) of BRCA1 (homologous recombination-HR) and DNA-PK (non-homologous end joining-NHEJ) two key double strand break repair (DSBR) proteins in the processing of non-DSB oxidatively induced single and clustered DNA lesions (OCDLs) in human gamma-irradiated tumor cells. In addition, chromosomal instability and apoptosis will be measured in each case. There are very limited and only fragmentary data on this specific field. Based also on preliminary data, our central hypothesis is that a compromised DSB repair pathway will also lead to deficient OCDL repair and accumulation of oxidatively-generated DNA lesions when DSBR deficient cells are challenged by various oxidizing agents like ionizing radiation. These studies are expected to provide meaningful mechanistic insights into DNA repair pathways involved in the processing of non-DSB clusters and therefore advance the field. They will also contribute to cancer etiology associated with complex DNA damage since accumulation of OCDLs is associated with increased mutation rate and chromosomal instability. Fingerprinting the molecular identity of these DNA modifications can be utilized in designing more efficient cancer therapeutic strategies based on the concept of selective apoptotic activation in malignant cells after exposure to therapeutic sources of oxidative stress like radiation and chemotherapy drugs
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 sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesnuclear physics
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesclinical medicineoncology
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Call for proposal
FP7-PEOPLE-2011-CIG
See other projects for this call
Coordinator
157 72 ATHINA
Greece