altered directionality in the creloxp sitespecific recombination pathway the sitespecific recombinase cre must employ control mechanisms to impose directionality on recombination when two recombination sites locus of crossing over in phage p1 loxp are placed as direct repeats on the same dna molecule collision between loxpbound cre dimers leads to excision of intervening dna if two sites are placed as inverted repeats the intervening segment is flipped around cre catalyzes these reactions in the absence of protein cofactors current models suggest that directionality is controlled at two steps in the recombination pathway the juxtaposition of loxp sites and the singlestrandtransfer reactions within the synaptic complex here we show that in escherichia coli strain 294cre directionality for recombination is altered when the expression of cre is increased this leads to deletion instead of inversion on substrates carrying two loxp sites as inverted repeats the nucleotide sequence composition of loxp sites remaining in aberrant products indicates that site alignment andor dna strand transfer in the in vivo creloxp recombination pathway are not always tightly controlled