DNA double-strand breaks formed by ionizing irradiation or other stresses are repaired by homologous recombination or DNA end-joining. This review focuses on the mechanism of double-strand break repair mediated by DNA end-joining, in which many factors have recently been identified. After DNA double-strand breakage, DNA end-joining takes place between the DNA ends that have nonhomologous sequences or very short regions ofhomology. The broken DNA is repaired if the DNA end-joining occurs in the same molecule, while it causes chromosome aberrations such as deletions, insertions, translocations and inversions if it occurs between different molecules. Rad50 and its relatives, Ku-proteins, DNA ligase VI and silencing factors, are involved in DNA end-joining in yeast and mammalian cells. These findings led us to propose a model in which the formation of a heterochromatin-like complex at broken ends is an important element in DNA end-joining.