A parallel DNA triplex as a model for the intermediate in homologous recombination

J Mol Biol. 1994 Jun 3;239(2):181-200. doi: 10.1006/jmbi.1994.1362.

Abstract

Parallel DNA triplexes considered to be putative intermediates in homologous recombination, are studied by means of theoretical conformational analysis. These triplexes are denoted as the R-form DNA. Two types of triplexes are analyzed: extended R-form DNA, modeling the triple standard structure, created transiently in the presence of recombination proteins (e.g. RecA); and collapsed R-form, obtained after deproteinization. These structures are stereochemically possible for any arbitrary sequence and have the following properties: (1) the third, R-strand, is parallel to the identical duplex strand and is located in the major groove of the duplex; (2) positions of all four bases in the R-strand are nearly isomorphic; (3) the proposed triplets are consistent with the chemical modification data for deproteinized DNA; we suggest, however, that they are the same in the RecA-DNA complex as well. Since the patterns of charges on each base of the R-strand are strictly complementary to the charges of the homologous Watson-Crick (WC) pair in the major groove, we propose that the selection of the homologous sequence may occur through these complementary electrostatic interactions (electrostatic recognition code). We demonstrate that in the collapsed triplex with a rise of about 3.4 A, the bases from the third R-strand can be inclined and interact with two WC base-pairs simultaneously, which could lead to recognition errors. These mispairings are unlikely in the extended triplex. Therefore, we speculate that a functional role of the extended and underwound DNA structure, transiently formed in the complex with RecA protein, is to obviate such errors and increase the stringency of recognition. In other words, RecA plays the role of a DNA chaperone facilitating the recognition of the single stranded DNA and the duplex. Finally, we show that the proposed isomorphic triplets are conformationally advantageous for strand exchange.

Publication types

  • Comparative Study

MeSH terms

  • Base Composition
  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics*
  • DNA, Single-Stranded / chemistry
  • Hydrogen Bonding
  • Models, Genetic*
  • Models, Molecular
  • Models, Structural
  • Nucleic Acid Conformation*
  • Rec A Recombinases / metabolism
  • Recombination, Genetic*
  • Thermodynamics
  • X-Ray Diffraction

Substances

  • DNA, Single-Stranded
  • DNA
  • Rec A Recombinases