Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes

Abstract

Significance The Smc5/6 complex plays multiple roles in DNA replication and repair. Its genome-protecting functions rely on its interaction with DNA; however, how this complex engages DNA is poorly understood. We report on a cryogenic electron microscopy structure of DNA-bound budding yeast Smc5/6 complex, revealing that its subunits form a clamp to encircle a double-helical DNA. We define the multi-subunit interactions forming the DNA clamp and the DNA binding sites distributed among subunits. We identify subunit transformations upon DNA capture and functional effects conferred by its multiple DNA contact sites. Our findings, in conjunction with studies on other structural maintenance of chromosomes (SMC) complexes, suggest a common SMC DNA-clamp mechanism with individual complex specific features that enable diverse genome organization and protection functions by SMC family complexes.