A human topoisomerase I cleavage complex is recognized by an additional human topisomerase I molecule in vitro
AUTOR(ES)
Søe, Kent
FONTE
Oxford University Press
RESUMO
Several recent studies have shown that human topoisomerase I (htopoI) can recognize various DNA lesions and thereby form a covalent topoisomerase I–DNA complex, which is known to be detrimental to cells. We have investigated whether htopoI recognizes another htopoI that is covalently trapped on a DNA substrate. For this purpose we created an artificial DNA substrate containing a specific topoisomerase I binding sequence, where the enzyme was trapped in the covalently bound form. We demonstrate that, in vitro, free htopoI stimulates the formation of an additional cleavage complex immediately upstream of the covalently bound topoisomerase I. The predominant distance between the two cleavage sites is 13 nt. In addition we find that these two enzymes may form direct protein–protein contacts and we propose that these may be mediated through the formation of a dimer by domain swapping involving the C-terminal and the core domains. Finally, we discuss the possibility that the double cleavage reaction may be the initial step for the removal of the recognized cleavage complex.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55829Documentos Relacionados
- Human topoisomerase I cleavage complexes are repaired by a p53-stimulated recombination-like reaction in vitro
- An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes.
- Human DNA topoisomerase I-mediated cleavage and recombination of duck hepatitis B virus DNA in vitro.
- Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.
- DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin