DNA double-strand breaks (DSB) are among the most lethal forms of DNA damage. DSBs are induced by a large number of endogenous and exogenous agents, as genotoxic chemicals and ionizing radiation, or due to replication of damaged DNA as well as collapse of a replication fork. DSB can either be properly repaired, restoring genomic integrity, or miss-repaired resulting in cell death, genomic instability, and cancer. Our group focuses on mechanisms of DSB repair using multi-disciplinary approach (biochemical, structural, computational, genetic, and single-molecule).