title: Human topoisomerase I cleavage complexes are repaired by a p53-stimulated recombination-like reaction in vitro.
abstract: Several studies have shown that human topoisomerase I (htopoI) cleaves in the vicinity of various DNA lesions and thereby forms covalent intermediates known as 'cleavage complexes'. Such complexes are detrimental to cells if they are not repaired. Therefore, it is generally accepted that repair pathways must exist for such lesions. We have demonstrated that a htopoI cleavage complex can be recognized by a second topoisomerase I molecule and thereby perform a so-called htopoI 'double cleavage' in vitro. In addition, we found that the double cleavage reaction was stimulated by p53. Here we show that the double cleavage reaction results in the removal of the original htopoI cleavage complex and the generation of a single-stranded gap of approximately 13 nt. This gap supports a sequence-dependent DNA recombination reaction mediated by the second htopoI molecule. Furthermore, we show that p53 strongly stimulates the recombination reaction. We suggest that this reaction may represent a novel p53-dependent topoisomerase I-induced recombination repair (TIRR) pathway for htopoI cleavage complexes.
authors.affiliation: Institute of Molecular Biotechnology, Department of Biochemistry, Beutenbergstrasse 11, D-07745 Jena, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stephan
authors.forename: Frank
authors.initials: F
authors.lastname: Grosse
authors.forename: Kent
authors.initials: K
authors.lastname: Søe
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D046911:Macromolecular Substances; D016159:Tumor Suppressor Protein p53; D004264:DNA Topoisomerases, Type I