A YEAST PROTEIN THAT BINDS TO VERTEBRATE TELOMERES AND CONSERVED YEAST TELOMERIC JUNCTIONS

We have identified three yeast proteins that bind to poly(C.A)/poly(T.G) repeats characteristic of telomeric sequences from yeast to human. TBF-alpha binds to the telomeric sequences of yeast, Tetrahymena, and vertebrates. In contrast, TBF-beta binds only to yeast telomeric sequences. Also identified was RAP1, the transcriptional silencer protein, which binds to a sequence motif found in upstream activating sequences (UASs) of a number of genes; the sequence motif also occurs frequently in yeast telomeric sequences. Because poly(C.A)/poly(T.G) sequences from a wide range of organisms will serve as the primer for the in vivo extension of telomeres in yeast, TBF-alpha is of particular interest. DNase I footprinting analysis indicated that TBF-alpha binds to the junction between the subtelomeric X sequence and poly(C1-3A) in a cloned yeast telomere. Examination of the junctions of known X sequences indicated that they all contain one or more repeats of CCCTAA, a sequence that is repeated in vertebrate telomeres. Earlier, Murray et al. (1988) reported that heterologous telomeric sequences positioned as far as several hundred base pairs from the termini of linear molecules can allow the addition of yeast telomeric sequences from nontelomeric termini in vivo. A possible function for TBF-alpha might be to serve as an anchoring protein for the yeast telomerase by binding to the conserved junction sequence at a distance from the terminus to allow addition of an irregular repeating sequence at the chromosome end.