Recombination repair and a treatment for BRCA2 tumours

A number of human diseases show a defect in homologous recombination (HR) and a predisposition to cancer or premature aging1,2. The involvement of HR in maintaining the stability of the genome may provide a link with the disease phenotype found in these patients1,3. Homologous recombination repair (HRR) is often referred to as an error-free repair pathway, and advantageous to the cell. However, recombination is a double-edged sword and may also result in loss of heterozygocity leading to inactivation of tumour suppressor genes, or cause gross gene rearrangements that can activate proto-oncogenes4,5. DNA double-strand breaks (DSBs) are known to be substrates for HRR in bacteria, yeast and mammals (see 3 for a review). However, it is reported that non-homologous end joining is the main pathway involved in repair of DSBs in mammalian cells6 and that HR is likely most important in repair of DSBs occurring at replication forks, for instance when a DNA single-strand break (SSB) is converted into a DSB during replication7. To maintain genomic integrity during replication, cells respond to DNA damage by activating signalling pathways that control repair of the damage and induce cell cycle delays. However, the coordination and connections between DNA repair and cell cycle delays ar