the covalent cleavage complex was trapped as described previously30 and purified by tandem cation - exchange and size - exclusion chromatography . crystals were grown by hanging - drop vapour diffusion , and diffraction data collected on bl8.3.1 ( advanced light source , lawrence berkeley national laboratory ) . initial phases were calculated by molecular replacement . for soaks , crystals were glutaraldehyde cross - linked in situ and exchanged into higher ph by vapour diffusion , prior to the addition of zncl2 . full methods and any associated references are available in the online version of the paper at www.nature.com/nature .
type ii topoisomerases are required for the management of dna tangles and supercoils1 , and are targets of clinical antibiotics and anti - cancer agents2 . 
 these enzymes catalyze the atp - dependent passage of one dna duplex ( the transport or t - segment ) through a transient , double - stranded break in another ( the gate or g - segment ) , navigating dna through the protein using a set of dissociable internal interfaces , or  gates3,4 . for more than 20 years 
 , it has been established that a pair of dimer - related tyrosines , together with divalent cations , catalyze g - segment cleavage57 . 
 recent efforts have proposed that strand scission relies on a  two - metal mechanism810 , a ubiquitous biochemical strategy that supports vital cellular processes ranging from dna synthesis to rna self - splicing11,12 . here 
 we present the structure of the dna - binding and cleavage core of saccharomyces cerevisiae topo ii covalently linked to dna through its active - site tyrosine at 2.5  resolution , revealing for the first time the organization of a cleavage - competent type ii topoisomerase configuration . 
 unexpectedly , metal - soaking experiments indicate that cleavage is catalyzed by a novel variation of the classic two - metal approach . 
 comparative analyses extend this scheme to explain how distantly - related type ia topoisomerases cleave single - stranded dna , unifying the cleavage mechanisms for these two essential enzyme families . 
 the structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular  trapdoor  to prevent subunit dissociation during cleavage . 
 this connection illustrates how an indispensable chromosome - disentangling machine auto - regulates dna - breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions .