Figure 1.

Two models for expansions of trinucleotide repeat tracts. (a) Expansion as a consequence of DNA polymerase slippage (4). During replication of a trinucleotide repeat tract (repeats indicated by rectangles), the primer and template strands transiently dissociate (step 1). Reassociation occurs with a DNA loop formed in the primer strand (step 2). Continued synthesis with no repair of the loop (step 3) would result in an addition of repeats. We show the loop stabilized by formation of a hairpin structure. (b) Expansion of a trinucleotide repeat tract as a consequence of displacement of an Okazaki fragment (5–7). In this model, synthesis displaces the 5′ end (indicated by ∗) of the neighboring Okazaki fragment (step 1′). The displaced strand folds back on itself to form a hairpin (step 2′) and is resistant to processing by FEN1 endonuclease (8). Continued synthesis and ligation (step 3′) results in an expanded trinucleotide repeat tract.