9 research outputs found
Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignment
Homologous gene shuffling between DNA promotes genetic diversity and is an
important pathway for DNA repair. For this to occur, homologous genes need to
find and recognize each other. However, despite its central role in homologous
recombination, the mechanism of homology recognition is still an unsolved
puzzle. While specific proteins are known to play a role at later stages of
recombination, an initial coarse grained recognition step has been proposed.
This relies on the sequence dependence of the DNA structural parameters, such
as twist and rise, mediated by intermolecular interactions, in particular
electrostatic ones. In this proposed mechanism, sequences having the same base
pair text, or are homologous, have lower interaction energy than those
sequences with uncorrelated base pair texts; the difference termed the
recognition energy. Here, we probe how the recognition energy changes when one
DNA fragment slides past another, and consider, for the first time, homologous
sequences in antiparallel alignment. This dependence on sliding was termed the
recognition well. We find that there is recognition well for anti-parallel,
homologous DNA tracts, but only a very shallow one, so that their interaction
will differ little from the interaction between two nonhomologous tracts. This
fact may be utilized in single molecule experiments specially targeted to test
the theory. As well as this, we test previous theoretical approximations in
calculating the recognition well for parallel molecules against MC simulations,
and consider more rigorously the optimization of the orientations of the
fragments about their long axes. The more rigorous treatment affects the
recognition energy a little, when the molecules are considered rigid. However
when torsional flexibility of the DNA molecules is introduced, we find
excellent agreement between analytical approximation and simulation.Comment: Paper with supplemental material attached. 41 pages in all, 4 figures
in main text, 3 figures in supplmental. To be submitted to Journa
Helical coherence of DNA in crystals and solution
The twist, rise, slide, shift, tilt and roll between adjoining base pairs in DNA depend on the identity of the bases. The resulting dependence of the double helix conformation on the nucleotide sequence is important for DNA recognition by proteins, packaging and maintenance of genetic material, and other interactions involving DNA. This dependence, however, is obscured by poorly understood variations in the stacking geometry of the same adjoining base pairs within different sequence contexts. In this article, we approach the problem of sequence-dependent DNA conformation by statistical analysis of X-ray and NMR structures of DNA oligomers. We evaluate the corresponding helical coherence length—a cumulative parameter quantifying sequence-dependent deviations from the ideal double helix geometry. We find, e.g. that the solution structure of synthetic oligomers is characterized by 100–200 Å coherence length, which is similar to ∼150 Å coherence length of natural, salmon-sperm DNA. Packing of oligomers in crystals dramatically alters their helical coherence. The coherence length increases to 800–1200 Å, consistent with its theoretically predicted role in interactions between DNA at close separations