DNA repreats in the human genome

摘要

Repetitive DNA sequences, interspersed through out the human genome, are capable of forming a wide variety of unusual DNA structures with simple and complex loopfolding patterns. The hairpin formed by the fragile X repeat, (CCG)_n, and the bipartite triplex formed by the Friedreich's ataxia repeat, (GAA)_n/(TTC)_n, show simple loopfolding. On the other hand, the doubly folded hairpin formed by the human centromeric repeat, (AATGG)_n, the hairpin G-quartet formed by (TTAGGG)_n at the 3'telomere overhang, and the hairpin G-quartet, and hairpin C~+.C paired i-motif formed by the insulin minisatellite, { ACAG_4AGTG_4 TGTC_4ACAC_4 }_n, show multiple and complex loopfolding. We have performed high resolution nuclear magnetic resonance (NMR ) spectroscopy and in vitro replication to show that unique base-pairing and loopfolding render stability to these unusual structures under physiological conditions. The formation of such stable structures offers a mechanism of unwinding which is advantageous during transcription. For example, the formation of the hairpin G-quartet, and hairpin C~+.C paired i-motif upstream of the insulin gene may facilitate transcription. These unusual DNA structures also provide unique "protein recognition motifs" quite different from a Watson-Crick double helix.