Checkpoint and recombination pathways independently suppress rates of spontaneous homology-directed chromosomal translocations in budding yeast.

Homologous recombination between short repeated sequences, such as Alu sequences, can generate pathogenic chromosomal rearrangements. We used budding yeast to measure homologous recombination between short repeated sequences located on non-homologous chromosomes to identify pathways that suppress spontaneous and radiation-associated translocations. Previous published data demonstrated that genes that participate in -mediated G arrest, the S phase checkpoint, and recombinational repair of double-strand breaks (DSBs) suppressed ectopic recombination between small repeats. We determined whether these pathways are independent in suppressing recombination by measuring frequencies of spontaneous recombination in single and double mutants. In the wild-type diploid, the rate of spontaneous recombination was (3 ± 1.2) × 10. This rate was increased 10-30-fold in the , , mutants, seven-fold in the checkpoint mutant, and 23-fold in the S phase checkpoint mutant. Double mutants defective in both and in either , , or increased spontaneous recombination rates by ∼40 fold, while double mutants defective in both the (ATR/ATM ortholog) and genes increased rates ∼100 fold. Compared to frequencies of radiation-associated translocations in wild type, radiation-associated frequencies increased in , , , , and diploid mutants; an increase in radiation-associated frequencies was detected in the diploid after exposure to 100 rads X rays. These data indicate that the S phase and G checkpoint pathways are independent from the recombinational repair pathway in suppressing homology-directed translocations in yeast.