Simultaneous induction of multiple mutations by N-methyl-N′-nitro-N-nitrosoguanidine in the yeast Saccharomyces cerevisiae

Summary Contrary to what happens in bacteria, mutations induced by nitrosoguanidine in yeast are not accompanied by an excess of mutations in nearby genes. We have investigated nitrosoguanidine mutagenesis in three regions of the yeast genome: the contiguous DNA segments HIS4A, HIS4B and HIS4C, located on chromosome III; ADE1 and CDC15 separated by about 3 map units on chromosome I; and CAN1, some 50 map units away from the centromere on chromosome V. Revertants at HIS4C never suffered mutations at HIS4A or HIS4B. Reversion at CDC15 did not affect the frequency of mutation at ADE1. No tsm mutations, leading to thermonsensitivity, were found in the immediate vicinity of the locus CAN1 after selecting for canavanine resistant mutants. However, as expected from nitrosoguanidine mutagenesis of replication points and the fixed pattern of chromosome replication, the induced tsm mutations seem not to map randomly over the yeast genome; in fact, two out of the three groups of such tsm mutations studied are located in the same chromosome arm as CAN1, indicating that these two regions are replicated at the same time as CAN1. Replication synchrony is less than perfect, since the tsm mutations of each group affect many different genes.