Clamping of DNA shuts the condensin neck gate

Condensin is a structural maintenance of chromosomes (SMC) complex needed for the compaction of DNA into chromatids during mitosis. Lengthwise DNA compaction by condensin is facilitated by ATPase-driven loop extrusion, a process that is believed to be the fundamental activity of most, if not all, SMC complexes. In order to obtain molecular insights, we obtained electron cryomicroscopy structures of yeast condensin in the presence of a slowly hydrolyzable ATP analog and linear as well as circular DNAs. The DNAs were shown to be clamped between the engaged heterodimeric SMC ATPase heads and the Ycs4 subunit, in a manner similar to previously reported DNA-bound SMC complex structures. Ycg1, the other non-SMC subunit, was only flexibly bound to the complex, while also binding DNA tightly and often remaining at a distance from the head module. In the clamped state, the DNA is encircled by the kleisin Brn1 and the two engaged head domains of Smc2 and Smc4. The Brn1/Smc2/Smc4 tripartite ring is closed at all interfaces, including at the neck of Smc2. We show that the neck gate opens upon head engagement in the absence of DNA, but it remains shut when DNA is present. Our work demonstrates that condensin and other SMC complexes go through similar conformations of the head modules during their ATPase cycle. In contrast, the behavior of the Ycg1 subunit in the condensin complex might indicate differences in the implementation of the extrusion reactions, and our findings will constrain further mechanistic models of loop extrusion by SMC complexes.

Automated summary

The condensin complex is responsible for compacting DNA into chromatids during mitosis. This study provides molecular insights into the structural dynamics of the complex and reveals differences in the behavior of its subunits. The findings will contribute to our understanding of the mechanism of DNA compaction by SMC complexes.