(CGA)(4): parallel, anti-parallel, right-handed and left-handed homoduplexes of a trinucleotide repeat DNA

Conformational properties of microsatellite DNA regions are the probable re ason of their expansions in genomes which lead to serious genetic diseases in some cases. Using CD spectroscopy, W absorption spectroscopy and polyacr ylamide gel electrophoresis, we study in this paper conformational properti es of (CGA)(4) and compare them with those of (CAG)(4) - a related repeat. connected with Huntington's disease. We show that (CGA)(4) can adopt severa l distinct conformations in solution. Around neutral pH it forms a parallel -stranded homoduplex containing C+.C, G.G, and A.A base pairs. Under the sa me conditions (CAG)(4) forms a hairpin. At slightly alkaline pH values and low ionic strength, (CGA)(4) also folded into a hairpin which transformed i nto a bimolecular anti-parallel homoduplex at increasing salt concentration s. The duplex easily isomerized into left-handed Z-DNA, implying that the m ismatched adenines between G.C pairs facilitate rather than hinder the B-Z transition. No similar changes took place with (CAG)(4). Thus, the conforma tional repertoire of (CAG)(4) includes parallel. anti-parallel, right-hande d, and left-handed homoduplexes. In contrast, (CAG)(4) invariably adopts on ly a single conformation. namely the very stable hairpin. (C) 2001 Elsevier Science B.V. All rights reserved.