STRUCTURES OF SOME POLY(PURINE).POLY(PYRIMIDINE) NUCLEIC ACIDS (FIBER DIFFRACTION, DNA-RNA HYBRIDS, POLYPURINE, POLYPYRIMIDINE)

HYE-SHIN CHUNG PARK, Purdue University

Abstract

X-ray diffraction studies of DNA-RNA double helices from fibers and an oligonucleotide crystal showed that the commonest structures for these hybrids are A-like. The diffraction patterns from poly dA.poly rU and poly dI.poly rC indicate that they may have unconventional structures, and show that the molecules in their fibers are uniaxially oriented with respectively 11(,1) and 10(,1) helical symmetry resulting in few Bragg reflections and much more continuous diffraction intensity. Quantitative analyses of these patterns and the modelling and refinement of the structures using the Linked-Atom-Least-Squares (LALS) method established that both hybrids have the heteromerous duplex structures with the DNA purine chains B-like and the RNA pyrimidine chains A-like. The gross morphologies of the heteromerous hybrids are more like that of A'-RNA rather than B-DNA, but different in detail. These distinct heteromerous structures may have a biological significance such as in the termination of transcription. In contrast to the symmetric palindromes, DNAs with poly(purine).poly(pyrimidine) sequences display a highly asymmetric distribution of purines and pyrimidines. Analyses of two types of diffraction patterns, (alpha) (hexagonal) and (beta)(,2) (monoclinic) from poly dA.poly dT showed that B-like structures with C2'-endo furanoses in both strands are significantly superior to the rest of models. Torsion angles of these B-like structures are very similar to those of B-DNA but the gross morphologies of duplexes are remarkably different mainly due to the shorter axial rise per residue and the negative tilt of the bases in pair. Analyses of two (alpha)-patterns from poly d(AI).poly d(CT) and poly dA.poly dU showed that the structures for these poly(purine).poly(pyrimidine) sequences belong to the same category as that of poly dA.poly dT. When the relative humidity was lowered, fibers of poly dA.poly dT, poly d(AI).poly d(CT) and poly dA.poly dU failed to undergo the B-to-A transition maintaining duplex conformation. Other polycrystalline diffraction patterns from poly d(AI).poly d(CT) obtained were (beta)(,1) (pseudo-orthorhombic) and (beta)(,2), whereas only (beta)(,1) form was found from poly dA.poly dU. Unit cell dimensions for each diffraction pattern vary slightly depending on the base composition.

Degree

Ph.D.

Subject Area

Biology

COinS