Circular, but not circularly permuted, deoxyribonucleic acid reacts slower than linear deoxyribonucleic acid with complementary linear deoxyribonucleic acid.

The electron microscope was used to count the number of double-stranded linear and circular renaturation products of a 2:1 by weight mixture of restricted double-stranded linear phi X174 RFI and single-stranded circular phi X174 viral deoxyribonucleic acid (DNA). More linear molecules than circular molecules are observed. However, when a 1:1 mixture of aliquots of either phi X174 RFI or SV40 DNA, each previously cleaved with a different single-site restriction enzyme, is denatured and renatured under conditions which assure circularization with out of phase molecules, an equal number of linear and circular molecules is observed. These experiments indicate that the nucleation rate is not affected by circular permutation of linear strands but is decreased approximately 3-fold when one of the reacting strands is circular. An excluded volume theory is developed which is consistent with these as well as previous results concerning the effects of DNA strand lengths on renaturation rates.