An Enzyme-Catalyzed Multistep DNA Refolding Mechanism in Hairpin Telomere Formation

Hairpin telomeres of bacterial linear chromosomes are generated by a dna cutting-rejoining enzyme protelomerase. protelomerase resolves a concatenated dimer of chromosomes as the last step of chromosome replication,converting a palindromic dna sequence at the junctions between chromosomes into covalently closed hairpins. the mechanism by which protelomerase transforms a duplex dna substrate into the hairpin telomeres remains largely unknown. we report here a series of crystal structures of the protelomerase tela bound to dna that represent distinct stages along the reaction pathway. the structures suggest that tela converts a linear duplex substrate into hairpin turns via a transient strand-refolding intermediate that involves dna-base flipping and wobble base-pairs. the extremely compact di-nucleotide hairpin structure of the product is fully stabilized by tela prior to strand ligation,which drives the reaction to completion. the enzyme-catalyzed,multistep strand refolding is a novel mechanism in dna rearrangement reactions. © 2013 shi et al.