In the presence of adenosine 5'-[gamma-thio]triphosphate, a nonhydrolyzable analog of ATP, Escherichia coli recA protein extensively unwinds duplex DNA in a reaction that is strongly stimulated by either homologous or heterologous single-stranded DNA [Cunningham, R.P., Shibata, T., DasGupta, C. & Radding, C.M. (1979) Nature (London) 281, 191-195]. In the presence of ATP and homologous circular single-stranded DNA, recA protein also unwinds circular duplex DNA that is nicked at a heterologous site. When DNA ligase seals this nick, the product is a highly negatively superhelical molecule that can be relaxed by E. coli topoisomerase I. This unwinding requires a high degree of homology since phi X174 single-stranded DNA does not serve as a cofactor in the unwinding of G4 DNA, even though these molecules are 70% homologous. Like synapsis itself, and unlike strand exchange which follows synapsis, unwinding is sensitive to inhibition by ADP. Because recA protein unwinds duplex DNA when neither the single-stranded DNA nor the duplex DNA has a free end in the region of homology, unwinding can be initiated or mediated by a synaptic structure that differs from that of a simple D loop. The paired circular single strand in the synaptic structure behaves like one strand of an under-wound helix because E. coli topoisomerase I can interwind it with its complement.

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