Clonal lethality caused by the yeast plasmid 2 mu DNA.

Strains of Saccharomyces that carry the nib allele of a nuclear gene exhibit a "nibbled" colony morphology if they also harbor the plasmid 2 mu DNA. I have found that the expression of the nibbled phenotype is correlated with the presence of a subpopulation of abnormally large cells that give rise to mortal clones. Large cells apparently become large as a consequence of a defect in DNA replication or nuclear division. Large nib cells contain twice as much 2 mu DNA per microgram of total DNA as small nib cells do, and elevated 2 mu DNA copy number is the cause, not the effect, of increased cell size. It appears that the NIB allele can prevent an increase in 2 mu DNA copy number, but cannot produce a decrease once the copy number has exceeded the normal level. I propose, therefore, that the NIB gene product normally represses the amplification of 2 mu DNA copy number, and that the nib allele is partially defective in this function.