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Cohesin complex with loader gripping DNA
Structural highlights
FunctionRAD21_SCHPO Cleavable component of the cohesin complex, involved in chromosome cohesion during cell cycle. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At metaphase-anaphase transition, this protein is cleaved by cut1 and dissociates from chromatin, allowing sister chromatids to segregate. Also involved in the DNA double-strand-break (DSB) repair system.[1] [2] Publication Abstract from PubMedDespite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here we combine biochemical approaches and cryoelectron microscopy (cryo-EM) to visualize a cohesin loading intermediate in which DNA is locked between two gates that lead into the cohesin ring. Building on this structural framework, we design experiments to establish the order of events during cohesin loading. In an initial step, DNA traverses an N-terminal kleisin gate that is first opened upon ATP binding and then closed as the cohesin loader locks the DNA against the ATPase gate. ATP hydrolysis will lead to ATPase gate opening to complete DNA entry. Whether DNA loading is successful or results in loop extrusion might be dictated by a conserved kleisin N-terminal tail that guides the DNA through the kleisin gate. Our results establish the molecular basis for cohesin loading onto DNA. A Structure-Based Mechanism for DNA Entry into the Cohesin Ring.,Higashi TL, Eickhoff P, Sousa JS, Locke J, Nans A, Flynn HR, Snijders AP, Papageorgiou G, O'Reilly N, Chen ZA, O'Reilly FJ, Rappsilber J, Costa A, Uhlmann F Mol Cell. 2020 Jul 30. pii: S1097-2765(20)30503-7. doi:, 10.1016/j.molcel.2020.07.013. PMID:32755595[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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