BRANCH MIGRATION THROUGH DNA-SEQUENCE HETEROLOGY

Branch migration of a DNA Holliday junction is a key step in genetic r ecombination. Previously, it was shown that a single base-pair heterol ogy between two otherwise identical DNA sequences is a substantial bar rier to passage of a Holliday junction during spontaneous branch migra tion. Here, we exploit this inhibitory effect of sequence heterology t o estimate the step size of branch migration. We also devise a simulat ion of branch migration through mismatched base-pairs to arrive at the underlying molecular basis for the block to branch migration imposed by sequence heterology. Based on the observation that two adjacent seq uence heterologies exert their effects on branch migration more or les s independently, we conclude that the step size of branch migration is quite small, of the order of one or two base-pairs per migratory step . Comparison of branch migration experiments through a single base-pai r heterology with simulations of a random walk through sequence hetero logy suggests that the inhibition of branch migration is largely attri butable to a thermodynamic barrier arising from the formation of unpai red or mispaired bases in heteroduplex DNAs. (C) 1998 Academic Press L imited.