ABSTRACT

DNA double-strand breaks (DSBs) are one of the most cytotoxic forms of DNA damage and disrupt the genomic integrity of a cell (1-5). DNA double-strand breaks can occur as products of ionizing radiation and genotoxic agents (6). However, the most frequent source of DSBs is DNA replication (7,8). Finally, DSBs are also generated by enzymatic activities, such as Spo11 in meiotic DNA recombination (9), Rag1/Rag2 in the generation of antibody and T-cell receptor diversity (10), and HO endonuclease in yeast mating-type switching (11). In these processes, DSBs are important cell physiological intermediates.