The structure of a stable intermediate in the A ↔ B DNA helix transition

Abstract

The DNA dodecamer CATGGGCCCATG in a crystal structure of resolution 1.3 Å has a conformation intermediate between A and B DNA. This trapping of a stable intermediate suggests that the A and B DNA families are not discrete, as previously believed. The structure supports a base-centered rather than a backbone-centered mechanism for the A 7 B transition mediated by guanine tracts. Interconversion between A and B DNA provides another means for regulating protein-DNA recognition.

DNA Structure: Alphabet Soup for the Cellular Soul

“…In this case, the inclination associated with the roll and tilt of the base pairs, in conjunction with the helical twist result in a shortening of the vertical distance between base pairs along the helical axis, even though the stacking distance remains 3.4 Å. Indeed, A-like DNAs that have little or no roll and tilt have helical rises that are ~3.4 Å, as expected (Ng et al, 2000;Vargason et al, 2001). Base pair parameters include those that relate the position or orientation of the base pair relative to the helical axis (inclination, x-displacement, and y-displacement), or the orientation and positions of the two bases in a pair (propeller twist, shear, stagger, stretch, buckle).…”

DNA Structural Similarity in the 2:1 Complexes of the Antitumor Drugs Trabectedin (Yondelis) and Chromomycin A3with an Oligonucleotide Sequence Containing Two Adjacent TGG Binding Sites on Opposing Strands

“…This effectively means that B-type nucleotides in the triplet region harboring the drug are paired with A/B-type nucleotides in the complementary strand. These altered sugar parameters correlate with the observed changes in slide and roll that are known to be necessary for the B3A transition (Ng et al, 2000;Vargason et al, 2001). Interactions between DNA and the Two Trabectedin Molecules Bonded in Opposite Strands.…”

“…All of these characteristics describe a DNA conformation (Ng et al, 2000;Vargason et al, 2001) that is intermediate between those of A-DNA and B-DNA (Table 2). On the other hand, both drugs span a common triplet DNA site, and the O8 atoms of chromomycin A 3 are involved in similar hydrogen bonding interactions with the exocyclic amino group (N2) of G4 and G12 as those observed between the methylendioxy oxygens of trabectedin and the N2 of G5 and G19.…”

“…For (trabectedin) 2 -d(GTATGGCCATAC) 2 , the energy-minimized average structure for TGGCCA was obtained from the last 4 ns of the MD simulations. Mean values for Aand B-DNA from X-ray crystal structures (Ng et al, 2000). …”

“…We have reported previously on the remarkable similarity in the manner in which trabectedin and zinc fingers from transcription factors such as EGR1/Zif268 or Sp1 (Marco et al, 2002) induce DNA structural distortions (Gago and Hurley, 2002), especially when three trabectedin molecules bind head-to-tail to three adjacent optimal binding sites on the same strand (Marco et al, 2002). In this case, trabectedin was shown to stabilize a DNA conformation that was intermediate between A-and B-form DNA (Ng et al, 2000).…”