TAILIEUCHUNG - Báo cáo Y học: Dynamic mechanism of nick recognition by DNA ligase

DNA ligases are the enzymes responsible for the repair of single-strandedanddouble-strandednicks ligases are structurally similar, possibly sharing a common molecular mechanism of nick recognition and ligation catalysis. This mechanism remains unclear, in part because the structure of ligase in complex with dsDNAhas yet to be ligases share common structural elementswith DNA polymerases, which have been cocrystallized with dsDNA. Based on the observed DNA polymerase–dsDNA interactions, we propose a mechanism for recognition of a single-stranded nick by DNA ligase | Eur. J. Biochem. 269 5993-5999 2002 FEBS 2002 doi REVIEW ARTICLE Dynamic mechanism of nick recognition by DNA ligase Alexei V. Cherepanov and Simon de Vries Kluyver Department of Biotechnology Delft University of Technology Delft the Netherlands DNA ligases are the enzymes responsible for the repair of single-stranded and double-stranded nicks in dsDNA. DNA ligases are structurally similar possibly sharing a common molecular mechanism of nick recognition and ligation catalysis. This mechanism remains unclear in part because the structure of ligase in complex with dsDNA has yet to be solved. DNA ligases share common structural elements with DNA polymerases which have been cocrystallized with dsDNA. Based on the observed DNA polymerase-dsDNA interactions we propose a mechanism for recognition of a single-stranded nick by DNA ligase. According to this mechanism ligase induces a B-to-A DNA helix transition of the enzyme-bound dsDNA motif which results in DNA contraction bending and unwinding. For non-nicked dsDNA this transition is reversible leading to dissociation of the enzyme. For a nicked dsDNA substrate the contraction of the enzyme-bound DNA motif a triggers an opened-closed conformational change of the enzyme and b forces the motif to accommodate the strained A B-form hybrid conformation in which the nicked strand tends to retain a B-type helix while the non-nicked strand tends to form a shortened A-type helix. We propose that this conformation is the catalytically competent transition state which leads to the formation of the DNA-AMP intermediate and to the subsequent sealing of the nick. Keywords DNA ligase nick recognition A-form DNA A B-form DNA hybrid protein-DNA interactions B-A DNA helix transition. DNA ligases are the enzymes that catalyze the joining of single- and double-stranded nicks in dsDNA 1 . These enzymes play a pivotal role in replication sealing the nicks in the lagging DNA strand 2-5 . They also participate .

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