Mechanism of catalysis by eukaryotic DNA topoisomerase I.
The elucidation of the chemistry of the topo I reaction has provided the first example of how a phosphodiester bond in DNA can be temporarily broken and the energy for reclosure stored in a covalent linkage between the end of the broken strand and the enzyme (Champoux, 1977a, 1981). This type of reaction offers several advantages to the cell. First, unnecessary exposure of DNA ends to nucleolytic attack is prevented. Second, breakage and reclosure of DNA strands can occur without an expenditure of ATP energy. Third, the combined breakage and rejoining reactions can be both spatially and temporally coordinated with other cellular activities by regulating the activity of a single protein molecule. This general mechanism has not only been extended to type II topoisomerases (see Chapters 3 and 5), but also to the specialized single-stranded phage replication proteins (e.g., phi X174 gene A protein) (Ikeda et al., 1976; Eisenberg et al., 1977) and to site-specific recombinases such as the bacteriophage lambda integrase (Craig and Nash, 1983), the delta gamma and Tn3 resolvases (Reed, 1981; Reed and Grindley, 1981; Krasnow and Cozzarelli, 1983; Hatfull and Grindley, 1986), and the yeast 2-microns circle FLP recombinase (Andrews et al., 1985; Gronostajski and Sadowski, 1985). Since the site-specific recombinases attach the broken strand to a different terminus rather than simply restoring the original phosphodiester bond as conventional topoisomerases do, they have been referred to as DNA strand transferases. It is conceivable that a similar mechanism applies to the rearrangement of immunoglobulin genes (Schatz et al., 1990) and to other specific genomic rearrangements that might occur during development (Matsuoka et al., 1991).
Champoux
J J
JJ
Department of Microbiology, School of Medicine, University of Washington, Seattle 98195.
D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002467:Cell Nucleus / Q000201:enzymology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data
D004264:DNA Topoisomerases, Type I