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Content archived on 2024-06-18

Processing of oxidatively induced clustered DNA lesions under a double strand break repair deficiency in human tumor cells

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)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2011-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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

ETHNICON METSOVION POLYTECHNION
EU contribution
€ 100 000,00
Address
HEROON POLYTECHNIOU 9 ZOGRAPHOU CAMPUS
157 72 ATHINA
Greece

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Region
Αττική Aττική Κεντρικός Τομέας Αθηνών
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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