SEQUENCE-SPECIFIC DNA RECOGNITION BY THE MYB-LIKE DOMAIN OF THE HUMANTELOMERE BINDING-PROTEIN TRF1 - A MODEL FOR THE PROTEIN-DNA COMPLEX

Telomeres consist of tandem arrays of short G-rich sequence motifs pac kaged by specific DNA binding proteins. In humans the double-stranded telomeric TTAGGG repeats are specifically bound by TRF1 and TRF2. Alth ough telomere binding proteins from evolutionarily distant species are not sequence homologues, they share a Myb-like DNA binding motif. Her e we have used gel retardation, primer extension and DNase I footprint ing analyses to define the binding site of the isolated Myb-like domai n of TRF1 and present a three-dimensional model for its interaction wi th human telomeric DNA. Our results suggest that the Myb-like domain o f TRF1 recognizes a binding site centred on the sequence GGGTTA and th at its DNA binding mode is similar to that of the homeodomain-like mot ifs of the yeast telomere binding protein RAP1. The implications of th ese findings for recognition of telomeric DNA in general are discussed .