Research Overview

Cellular responses to DNA damage
The genomes of eukaryotic cells are under continuous assault by cosmic and terrestrial radiation sources, as well as the byproducts of the intracellular metabolism such as reactive oxygen species and replication errors that lead to the generation of DNA double strand breaks (DSBs). In addition to accidental events, DSBs are also generated during scheduled biological processes such as meiosis or V(D)J recombination and during diagnostic procedures utilizing ionizing radiation. Finally, therapeutic interventions in the therapy of cancer, such as exposure to ionizing radiation and treatment with certain chemotherapeutic agents, leads to the generation of DSBs. DSBs are severe lesions with a high probability of conversion to lethal or mutagenic events. Therefore, eukaryotic cells have developed efficient repair pathways to remove DSBs from their genome. These repair activities are supported by signaling pathways, termed checkpoints that register the presence of DSBs and arrest or delay cell cycle progression in G1, S, or G2 phase to prevent modifications compromising repair or generating lethal events.

• Evaluation of the relative contribution of the different pathways implicated in double strand break repair
• Elucidation of the contribution of checkpoints in double strand break repair
• Molecular mechanisms of hyperthermia induced checkpoint activation
• Radiation effects in mouse embryonic tissue with emphasis on genomic instability

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