STRUCTURE & FUNCTION OF NON-WATSON-CRICK TELOMERIC DNA

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Chromosome stability is crucial for the faithful passage of genetic information at each cell division. Telomeres are structures at chromosomal termini that are essential for chromosome stability. All telomeric DNA contains simple, G/C-rich, repeated sequences in which the G and C residues are segregated to opposite strands of the duplex. The G-rich strand of all telomeres examined extends beyond the duplex at the molecular terminus of the telomere. In vitro, all telomeric G-rich strands tested can self-associate by non-Watson-Crick (G-G and G-T) base pairing. Taken together, these data suggest that the G-strand overhang forms a self-associated structure in vivo and that this structure is intimately involved in telomere function. The goal of this project is to understand how telomeres confer stability to chromosomes and, more specifically, what the role(s) of the unique G- strand DNA structure is (are) in accomplishing this. The specific aims are: 1) to determine the molecular details of the G-strand structure, 2) to ascertain the biological function of the telomeric G-strand structure using in vitro and in vivo assays and to determine if non-Watson-Crick base paired structures can form in a Watson-Crick Environment, 3) to characterize an activity we have identified that binds specifically to the G-strand structure, 4) to produce monoclonal antibodies that react with the G-strand structure and 5) to explore telomere location and dynamics in fixed and living cells by fluorescence and electron microscopy.