The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

FP6 priority
1.1.1   Genomics and Biotechnology for Health
Title of the proposal

DNA double-strand break repair in eukaryotes

Slovak Academy of Sciences, Cancer Research Institute
Vlarska 7, 833 91 Bratislava, Slovak Republic
+421 2 59327 333

Research subject for a potential FP6 project

DNA double-strand breaks (DSBs) are perharps the most deleterious DNA lesions as they disrupt both DNA strands causing problems for all DNA transactions. DSBs can be induced by exogenous agents such as ionising radiation and chemicals as well as as by endogenous sources such as free radical generated during metabolic processes. If unrepaired DSBs can result in loss of genomic material, if misrepaired, they can cause genomic rearrangements, both events that can lead to carcinogenesis. In general, there are two pathways for DSB repair, homologous recombination (HR) and non-homologous end-joining (NHEJ). Both systems have been shown to be active in the yeast Saccharomyces cerevisiae. Firstly, the project is undertaken to find out which DSB repair mechanism might involve S. cerevisiae SNM1/PSO2 gene product, a protein known to be acting upon ICL-associated DSBs. A possible interaction of Pso2/Snm1 with the main yeast HR and NHEJ proteins will be examined using both a genetic and biochemical approaches. Secondly, the DNA repair of oxidative damage by base excision repair pathway will be studied in yeast. Moreover, the possible role(s) of the S.cerevisiae RAD51 and RAD52 gene products, the key proteins involved in DSB repair by HR, in the repair of oxidative damage-induced DSBs will be examined.

Recent international cooperation of the research team

- Joao A.P. Henriques, Centro de Biotecnologia, Universidade Federal Rio Grande do Sul, 91501/97 Porto Alegre-RS Brasil
- Ada Kolman, Department of Molecular Biology and Functional Genomics, Stockholm University, SE-106 91 Stockholm, Sweden
- Penny Jeggo a Anthony Carr, Genome Damage and Stability Centre, University of Sussex, Brighton, Falmer, BN1 9RR, Unitted Kingdom
- Serge Boiteux, CEA, Departement de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA Radiobiologie Moleculaire et Cellulaire, Fontenay aux Roses, France

Proposerīs relevant publications related to the research subject

Henriques J.A.P., Brozmanova J., Brendel M.: Role of PSO genes in the repair of photoinduced interstrand cross-links and photooxidative damage in the DNA of the yeast Saccharomyces cerevisiae. J. Photochem. Photobiol. B: Biol. 39, 185-196, 1997
Sigler K., Chaloupka J., Brozmanova J., Stadler N, Hofer M.: Oxidative stress in microorganbisms - I Microbial vs. higher cells - Damage and defenses in relation to cell aging and death. Folia Microbiol. 44, 587-624, 1999
Brozmanova J., Vlckova V., Farkasova E., Dudas A., Vlasakova D., Chovanec M., Mikulovska Z., Fridrichova I., Saffi J., Henriques J.A.P.: Increased DNA double strand breakage is repsonsible for sensitivity of the pso3-1 mutant of Saccharomyces cerevisiae to hydrogen peroxide. Mutation Res. 485, 345-355, 2001
Chovanec M., Cedervall B., Kolman A: DNA damage induced by gamma-radiation in combination with ethylene oxide in human diploid fibroblasts. Chem. Biol. Interactions, 373, 259-268 2001