Jin Yu, Taekjip Ha, and Klaus Schulten.
Conformational model of the Holliday junction transition deduced
from molecular dynamics simulations.
Nucleic Acids Research, 32:6683-6695, 2004.
(PMC: 545448)
YU2004
Homologous recombination plays a key role in the restart of
stalled replication forks and in the generation of genetic
diversity. During this process, two homologous DNA molecules
undergo strand exchange to form a four-way DNA (Holliday)
junction. In the presence of metal ions, the Holliday junction
folds into the stacked-X structure which has two alternative
conformers. Experiments have revealed spontaneous transitions
between these conformers, but their detailed pathways are not
known. Here we report a series of molecular dynamics simulations
of the Holliday junction at physiological and elevated (400 K)
temperatures. The simulations reveal new tetrahedral
intermediates and suggest a schematic framework for conformer
transitions. The tetrahedral intermediates bear resemblance to
the junction conformation in complex with a junction-resolving
enzyme, T7 endonuclease I, and indeed one intermediate forms a
stable complex with the enzyme as demonstrated in one
simulation. We also describe free energy minima for various
states of the Holliday junction system which arise during
conformer transitions. The results show that magnesium ions
stabilize the stacked-X form and destabilize the open and
tetrahedral intermediates. Overall, our study provides a
detailed dynamic model of the Holliday junction undergoing a
conformer transition.
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