By definition, homologous repair of damaged DNA requires a homologous sequence that can serve as the template for repair. We recently defined the “partner choice” for homologous repair in mammalian cells using molecular genetic approaches.
The discovery of a major role for homologous recombination as a DNA repair pathway implied that cell mutants isolated on the basis of sensitivity to certain DNA-damaging agents could have homologous repair defects.
BRCA1 and BRCA2 mutations are estimated to be responsible for 80 percent of familial breast cancers and more than 95 percent of familial ovarian cancers. The identification of the hereditary breast and ovarian cancer genes was met with great excitement and hope that the etiology of these diseases would be quickly understood.
Unlike its DNA repair role in somatic cells, homologous recombination has a distinct role in meiosis in ensuring proper chromosome segregation. In yeast, an early step of the meiotic program is the introduction of double-strand breaks into chromosomes by the Spo11 protein to promote recombination between homologs.