Genomic integrity and the repair of double-strand DNA breaks

The induction of double-strand breaks (DSBs) in DNA by exposure to DNA dama ging agents or as inter-mediates in normal cellular processes, creates a se vere threat for the integrity of the genome. Unrepaired or incorrectly repa ired DSBs lead to broken chromosomes and/or gross chromosomal rearrangement s which are frequently associated with tumor formation in mammals. To maint ain the integrity of the genome and to prevent the formation of chromosomal aberrations, several pathways exist in eukaryotes: homologous recombinatio n (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA) . These mechanisms are conserved in evolution, but the relative contributio n depends on the organism, cell type and stage of the cell cycle. In yeast, DSBs are primarily repaired via HR while in higher eukaryotes, both HR and NHEJ are important. In mammals, defects in both HR or NHEJ lead to a predi sposition to cancer and at the cellular level, the frequency of chromosomal aberrations is increased. This review summarizes our current knowledge abo ut DSB-repair with emphasis on recent progress in understanding the precise biochemical activities of individual proteins involved. (C) 2001 Elsevier Science B.V. All rights reserved.