DNA homology and chromosome stability: a sensitive yeast genetic system for identifying double-stranded DNA damage

Recombination is required for the repair of many types of lesions and it can be a source of genetic diversity. We are investigating the requirements for homology in recombination and the consequences of recombination between DNA divergent sequences. Recombination between sequences of partial homology could account for chromosome rearrangements leading to the generation of novel genes and possibly involved in initiating events in carcinogenesis. We have developed a method for examining the role of homology between a specific pair of chromosomes in "protecting" chromosomes against DNA damage (Resnick et al., 1989). In the yeast Saccharomyces cerevisiae DNA double-strand breaks (DSBs) induced in diploid G-1 cells are normally repaired by recombination between homologous chromosomes. When homology is greatly reduced the DSBs lead to chromosome loss. These observations suggest that the system that has been used to study the role of recombination in repair can also be used to measure double-strand damage at low biologically meaningful doses.