title: Topoisomerases and site-specific recombinases: similarities in structure and mechanism.
abstract: The processes of DNA topoisomerization and site-specific recombination are fundamentally similar: DNA cleavage by forming a phospho-protein covalent linkage, DNA topological rearrangement, and DNA ligation coupled with protein regeneration. Type IB DNA topoisomerases are structurally and mechanistically homologous to tyrosine recombinases. Both enzymes nick DNA double helices independent of metal ions, form 3'-phosphotyrosine intermediates, and rearrange the free 5' ends relative to the uncut strands by swiveling. In contrast, serine recombinases generate 5'-phospho-serine intermediates. A 180° relative rotation of the two halves of a 100 kDa terameric serine recombinase and DNA complex has been proposed as the mechanism of strand exchange. Here I propose an alternative mechanism. Interestingly, the catalytic domain of serine recombinases has structural similarity to the TOPRIM domain, conserved among all Type IA and Type II topoisomerases and responsible for metal binding and DNA cleavage. TOPRIM topoisomerases also cleave DNA to generate 5'-phosphate and 3'-OH groups. Based on the existing biochemical data and crystal structures of topoisomerase II and serine recombinases bound to pre- and post-cleavage DNA, I suggest a strand passage mechanism for DNA recombination by serine recombinases. This mechanism is reminiscent of DNA topoisomerization and does not require subunit rotation.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. wei.yang@nih.gov
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053837:DNA Cleavage; D004254:DNA Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism*; D026942:DNA Topoisomerases / Q000737:chemistry* / Q000378:metabolism*; D015870:Gene Expression; D011487:Protein Conformation; D012694:Serine; D014443:Tyrosine
chemical_list: D014443:Tyrosine; D012694:Serine; D004247:DNA; D004254:DNA Nucleotidyltransferases; C077570:Site-specific recombinase; D026942:DNA Topoisomerases