Abstract
This chapter discusses structure-functional analysis of expandable DNA repeats. Simple DNA repeats including, but not limited to H motifs, are called “suicidal sequences” for the DNA polymerization. The analysis of the replication fork progression through different expandable repeats in bacterial, yeast, and cultured mammalian cells, via 2-dimesional electrophoretic analysis of the replication intermediates reveals the suitability of this concept for in vivo. In all the three systems, these repeats attenuated DNA replication and there was a good agreement between the repeat instability and replication inhibition thresholds. The replication model for repeat expansions assume that expansions occur during multiple replication fork stalls and restarts within structure-prone repetitive runs. Formation of unusual DNA structures by H motifs during the DNA synthesis in vitro can also block even the most processive DNA polymerases. Interestingly, the polymerase itself triggered the formation of unusual DNA structures that subsequently inhibited it.
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