SPECIFIC DNA-REPLICATION MUTATIONS AFFECT TELOMERE LENGTH IN SACCHAROMYCES-CEREVISIAE

To investigate the relationship between the DNA replication apparatus and the control of telomere length, we examined the effects of several DNA replication mutations on telomere length in Saccharomyces cerevis iae. We report that a mutation in the structural gene for the large su bunit of DNA replication factor C (cdc44/rfc1) causes striking increas es in telomere length. A similar effect is seen with mutations in only one other DNA replication gene: the structural gene for DNA polymeras e alpha (cdc17/pol1) (M. J. Carson and L. Hartwell, Cell 42:249-257, 1 985), For both genes, the telomere elongation phenotype is allele spec ific and appears to correlate with the penetrance of the mutations. Fu rthermore, fluorescence-activated cell sorter analysis reveals that th ose alleles that cause elongation also exhibit a slowing of DNA replic ation, To determine whether elongation is mediated by telomerase or by slippage of the DNA polymerase, we created cdc17-1 mutants carrying d eletions of the gene encoding the RNA component of telomerase (TLC1). cdc17-1 strains that would normally undergo telomere elongation failed to do so in the absence of telomerase activity, This result implies t hat telomere elongation in cdc17-1 mutants is mediated by the action o f telomerase. Since DNA replication involves transfer of the nascent s trand from polymerase cy. to replication factor C (T. Tsurimoto and B. Stillman, J. Biol. Chem. 266:1950-1960, 1991; T. Tsurimoto and B. Sti llman, J. Biol. Chem, 266:1961-1968, 1991; S. Wage and B. Stillman, Na ture [London] 369:207-212, 1994), one possibility is that this step af fects the regulation of telomere length.