UNEQUAL FIDELITY OF LEADING-STRAND AND LAGGING-STRAND DNA-REPLICATIONON THE ESCHERICHIA-COLI CHROMOSOME

We have investigated the question whether during chromosomal DNA repli cation in Escherichia coli the two DNA strands may be replicated with differential accuracy. This possibility of differential replication fi delity arises from the distinct modes of replication in the two strand s, one strand (the leading strand) being synthesized continuously, the other (the lagging strand) discontinuously in the form of short Okaza ki fragments. We have constructed a series of lacZ strains in which th e lac operon is inserted into the bacterial chromosome in the two poss ible orientations with regard to the chromosomal replication origin or iC. Measurement of lac reversion frequencies for the two orientations, under conditions in which mutations reflect replication errors, revea led distinct differences in mutability between the two orientations. A s gene inversion causes a switching of leading and lagging strands, th ese findings indicate that leading and lagging strand replication have differential fidelity. Analysis of the possible mispairs underlying e ach specific base pair substitution suggests that the lagging strand r eplication on the E. coli chromosome may be more accurate than leading strand replication.