DSBR AND CLUSTERS
Processing of oxidatively induced clustered DNA lesions under a double strand break repair deficiency in human tumor cells
| Coordinatore | NATIONAL TECHNICAL UNIVERSITY OF ATHENS - NTUA
Organization address
address: HEROON POLYTECHNIOU 9 ZOGRAPHOU CAMPUS contact info |
| Nazionalità Coordinatore | Greece [EL] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2011-CIG |
| Funding Scheme | MC-CIG |
| Anno di inizio | 2012 |
| Periodo (anno-mese-giorno) | 2012-06-01 - 2016-05-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
NATIONAL TECHNICAL UNIVERSITY OF ATHENS - NTUA
Organization address
address: HEROON POLYTECHNIOU 9 ZOGRAPHOU CAMPUS contact info |
EL (ATHINA) | coordinator | 100˙000.00 |
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Obiettivo del progetto (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'