Structures of helical junctions in nucleic acids
Authors: Lilley David M. J. 
Published: July 2002

1. Introduction 1102. The occurrence of helical junctions in nucleic acids 1112.1 The four-way DNA junction and genetic recombination 1112.2 Helical junctions in RNA 1122.3 Homology and branch migration of four-way junctions 1122.4 Forms of helical junctions available for study 1133. The structure of the four-way DNA junction 1143.1 The global structure of the junction 1143.2 The stacked X-structure 1143.3 The junction has antiparallel character 1153.4 The stereochemistry of the four-way DNA junction 1163.4.1 Molecular modelling 1163.4.2 NMR studies 1163.4.3 Crystallography 1164. Role of metal ions in the folding of the four-way DNA junction 1224.1 An extended structure of the four-way junction at low salt concentrations 1224.2 Structural interconversion between the extended and stacked X-structures 1224.3 Location of structural metal ions in the four-way junction 1245. Conformational variation in the four-way junction 1255.1 Formation of alternative stacking conformers and sequence-dependent bias 1255.1.1 Demonstration of alternative stacking conformers 1255.1.2 Simultaneous presence of both stacking conformers 1265.1.3 Exchange between stacking conformers 1285.1.4 Longer-range sequence dependence 1295.2 Variability in the interhelical angle 1295.2.1 The interhelical angle 1295.2.2 Variation, flexibility and malleability of the interhelical angle 1305.3 Perturbation of the junction structure 1306. Branch migration 1316.1 Strand exchange between homologous sequences, and branch migration 1316.2 The rate of branch migration 1316.3 The effect of magnesium ions on branch migration rates 1326.4 Branch migration and the structure of the DNA junction 1327. Three-way DNA junctions 1337.1 The perfectly basepaired three-way junction 1337.2 The effect of unpaired bases; the bulged three-way junction 1347.3 Two inequivalent stacking conformers 1347.4 The stereochemistry of the bulged three-way junction 1368. Helical junctions in RNA 1368.1 The four-way junction in RNA 1368.2 Some important four-way junctions in functional RNA species 1378.2.1 The U1 snRNA junction 1378.2.2 The four-way junction of the hairpin ribozyme 1388.3 Three-way helical junctions in RNA 1389. Recognition and distortion of four-way DNA junctions by proteins 1399.1 Junction-resolving enzymes 1399.1.1 Occurrence of junction-resolving enzymes 1409.1.2 Cleavage of DNA junctions by resolving enzymes 1409.1.3 Structure-selective binding of resolving enzymes to four-way junctions 1439.1.4 Distortion of the structure of junctions by resolving enzymes 1439.1.5 Relationship between distortion and cleavage of DNA junctions 1449.2 Branch migration proteins 1459.3 Site-specific recombinases 1469.4 Other proteins 14910. Summary and conclusions 14911. Acknowledgements 15112. References 151Helical junctions in nucleic acids are important in biology. In DNA, their main significance
is as intermediates in both homologous and site-specific recombination events. In RNA they
are important architectural elements.Helical junctions may be defined as branchpoints where double-helical segments intersect
with axial discontinuities, such that strands are exchanged between the different helical
sections. Thus the integrity of junctions is maintained by the covalent continuity of the
component strands. Junctions can be perfectly basepaired, such that every base is paired with
its Watson–Crick complement, or they can contain mismatches or unpaired bases; the latter
can have significant effects on the folding of the structures. A systematic nomenclature exists
for the unambiguous description of different junctions (Lilley et al. 1995) and some examples
are illustrated in Fig. 1.The purpose of the present article is to review what is known about the structures of helical
junctions, and their recognition by proteins. The recent presentation of crystal structures of
four-way junctions (Nowakowski et al. 1999; Ortiz-Lombardía et al. 1999; Eichman et al.
2000) provides a good opportunity to examine the current state of knowledge. We can also
ask whether there are general principles behind the folding of branched nucleic acid species.
Two possible principles emerge.