Structural transition from dimeric to tetrameric i-motif, caused by the presence of TAA at the 3'-end of human telomeric C-rich sequence.

Widely dispersed in genomic DNA, the tandem C-rich repetitive stretches may fold below physiological pH, into i-motif structures, stabilized by C.C(+) pairing. Herein, structural status of a 9-mer stretch d(CCCTAACCC), [the truncated double repeat of human telomeric sequence], and its extended version, comprising of additional--TAA segment at the 3'-end, representing the complete double repeat d(CCCTAACCCTAA), has been investigated. The pH dependent monophasic UV-melting, Gel and CD data suggested that while the truncated version adopts a bimolecular i-motif structure, its complete double repeat (12-mer) sequence exists in two (bimolecular and tetramolecular) forms. A model is proposed for the tetramolecular i-motif with conventional C.C(+) base pairs, additionally stabilized by asymmetric A.A base pairs at the -3' TAA flanking ends and Watson-Crick A.T hydrogen bonding between intervening bases on antiparallel strands. Expanding the known topologies of DNA i-motifs, such atypical geometries of i-motifs may have implications in their recognition by proteins. Copyright 2009 Wiley Periodicals, Inc.