Structural polymorphism of homopurine-homopyrimidine sequences: the secondary DNA structure adopted by a d(GA.CT)22 sequence in the presence of zinc ions.

Abstract

In this paper, we have analysed the conformational behaviour shown by the homopurine–homopyrimidine alternating d(GA.CT)22 sequence cloned into SV40. Our results show that, in the presence of zinc ions, the d(GA.CT)22 sequence adopts an altered secondary DNA structure (*H‐DNA) which differs from either B‐DNA or H‐DNA. Formation of *H‐DNA is facilitated by negative supercoiling and does not appear to require base protonation, since it is induced at neutral pH by approximately 0.4 mM ZnCl2. The patterns of OsO4 and DEPC modification obtained in the presence of zinc are compatible with a homopurine–homopurine–homopyridimine triplex, though other structural models for *H‐DNA are also possible. The hypersensitivity to S1‐cleavage of the d(GA.CT)22 sequence is reinterpreted in terms of the equilibria between the B‐, H‐ and *H‐forms of the sequence. These results reveal the high degree of structural polymorphism shown by homopurine‐homopyrimidine sequences. Its biological relevance is discussed.

Towards a better understanding of the unusual conformations of the alternating guanine–adenine repeat strands of DNA

“…Tetraplexes are only formed by the (G + A) strands of DNA where guanine dominates. 21 This, for example, concerns (GGGA) 5 or (GGA) 7 but not (GGAA) 5 , (GAA) 7 , and (GAAA) 5 . 21 Our data are also not consistent with a hairpin dimer of (GA) n containing guanine tetrads, a conformation which was proposed on the basis of a UV resonance Raman study.…”

“…It is also informative that the homoduplex of (GA) n can coexist with a homoduplex of (TA) n in a single DNA molecule. 19 (GATA) 5 even can, as a whole, adopt either a homoduplex characteristic of (TA) 10 or (GA) 10 depending on the salt concentration, and switch between them reversibly. 19 We think that the starting structure to model the homoduplex of (GA) n should be sought in parallel-stranded pieces of crystal [35][36][37][38] or NMR solution 39,40 structures of purine-rich molecules of DNA.…”

“…1 They are involved in biological processes 2,3 such as DNA recombination, which is very likely a consequence of their peculiar structural properties. 3,4 They are known to form triplexes consisting of either two purine and one pyrimidine strands 5 in the presence of metal ions or two pyrimidine and one purine strands appearing at acidic pH. 6 Apart from triplexes, the (GA) n strands have long been known to self-associate and generate cooperatively melting structures even in the absence of the complementary pyrimidine strand.…”

Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments

“…Binding to the bases can destabilize DNA and cause local denaturation of the DNA double helix. It has been shown that some local DNA structures such as intramolecular triplexes (Beltran et al, 1993;Bernues et al, 1989), hairpins (Martinez-Balbas and Azorin, 1993) and homopurine duplexes (Ortiz-Lombardia et al, 1995) are stabilized by zinc. In the presence of zinc, formation of kinks in DNA molecules have been observed (Han et al, 1997a,b;Laundon and Gri th, 1987).…”

Parallel intramolecular DNA triple helix with G and T bases in the third strand stabilized by Zn2+ ions

“…Purine motif triple helices usually require the presence of divalent ions, but not all divalent ions have equivalent efficiencies. For instance Mg 2+ ions which have been used in the above recalled studies are unable to induce R•R.Y triplexes in d(GA.TC) n sequences (29) while Zn 2+ ions do (30). In many cases Zn 2+ ions have proved to be particularly efficient in antiparallel triple helix stabilization (31)(32)(33).…”