Structure of the cohesin loader Scc2

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The functions of cohesin are central to genome integrity, chromosome organization andtranscription regulation through its prevention of premature sister-chromatid separationand the formation of DNA loops. The loading of cohesin onto chromatin depends on theScc2–Scc4 complex; however, little is known about how it stimulates the cohesion-loadingactivity. Here we determine the large ‘hook’ structure of Scc2 responsible for catalysingcohesin loading. We identify key Scc2 surfaces that are crucial for cohesin loadingin vivo.With the aid of previously determined structures and homology modelling, we derivea pseudo-atomic structure of the full-length Scc2–Scc4 complex. Finally, using recombinantlypurified Scc2–Scc4 and cohesin, we performed crosslinking mass spectrometry andinteraction assays that suggest Scc2–Scc4 uses its modular structure to make multiplecontacts with cohesin