The integrity of the genome is crucial for tumour suppression and for the propagation of genomic information to subsequent generations. DNA damage can result from cellular metabolism or routine errors in DNA replication and recombination. In addition, exogenous genotoxic agents, such as ultraviolet light, oxidative stress and chemical mutagens, can lead to a range of nucleotide modifications and DNA breaks. To combat these attacks on the genome, cells have evolved a response system that induces cell cycle arrest, allowing sufficient time for specialized groups of proteins to repair the incurred damage. The DNA damage response system activates the appropriate DNA repair pathway or, in the case of irreparable damage, induces apoptosis.

Tremendous advances have occurred in the past decade, which have increased our understanding of the DNA damage response and the derivation of genomic rearrangements, both in mice and humans. This special Focus on Genome Instability highlights some of the key mechanisms devised to maintain genome integrity and discusses the potential outcomes of genome instability.

The Nature Research library contains other relevant articles, including Reviews, on the broad topic of genome instability.