TEL+CEN ANTAGONISM ON PLASMIDS INVOLVES TELOMERE REPEAT SEQUENCES TRACTS AND GENE-PRODUCTS THAT INTERACT WITH CHROMOSOMAL TELOMERES

In Saccharomyces cerevisiae, circular plasmids that include either a centromere (CEN-plasmids) or a telomere sequence (TEL-plasmids) segregate more efficiently than circular ARS-plasmids. In contrast, circular plasmids that include both telomere and centromere sequences were unstable, a property we term TEL+CEN antagonism. TEL+CEN antagonism required a telomere repeat tract longer than 49 bp although the distance and relative orientation of the centromere and telomere sequences was not critical. TEL+CEN antagonism was alleviated in strains carrying different rap1 alleles including rap1(ts), rap1(s), and rap1(t) alleles. Mutations SIR2, SIR3, SIR4, NAT1 and ARD1, genes that influence transcriptional silencing at telomeres and at the silent mating type loci, abolished TEL+CEN antagonism. Mutation of SIR1 also partially alleviated TEL-CEN antagonism. In some sir mutant strains short yeast artificial chromosomes (YACs), which are normally unstable, became more stable, suggesting that the same mechanism that caused TEL+CEN antagonism on circular plasmids may contribute to the instability of short linear plasmids.