{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Palle K"],"funding":["NCI NIH HHS"],"pagination":["27767-27775"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2562070"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["283(41)"],"pubmed_abstract":["In eukaryotes, DNA topoisomerase I (Top1) catalyzes the relaxation of supercoiled DNA by a conserved mechanism of transient DNA strand breakage, rotation, and religation. The unusual architecture of the monomeric human enzyme comprises a conserved protein clamp, which is tightly wrapped about duplex DNA, and an extended coiled-coil linker domain that appropriately positions the C-terminal active site tyrosine domain against the Top1 core to form the catalytic pocket. A structurally undefined N-terminal domain, dispensable for enzyme activity, mediates protein-protein interactions. Previously, reversible disulfide bonds were designed to assess whether locking the Top1 clamp around duplex DNA would restrict DNA strand rotation within the covalent Top1-DNA intermediate. The active site proxim"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Disulfide cross-links reveal conserved features of DNA topoisomerase I architecture and a role for the N terminus in clamp closure."],"pmcid":["PMC2562070"],"funding_grant_id":["CA58755","CA111542","CA21765"],"pubmed_authors":["Losasso C","Benedetti P","Bjornsti MA","Palle K","Pattarello L","van der Merwe M"],"additional_accession":[]},"is_claimable":false,"name":"Disulfide cross-links reveal conserved features of DNA topoisomerase I architecture and a role for the N terminus in clamp closure.","description":"In eukaryotes, DNA topoisomerase I (Top1) catalyzes the relaxation of supercoiled DNA by a conserved mechanism of transient DNA strand breakage, rotation, and religation. The unusual architecture of the monomeric human enzyme comprises a conserved protein clamp, which is tightly wrapped about duplex DNA, and an extended coiled-coil linker domain that appropriately positions the C-terminal active site tyrosine domain against the Top1 core to form the catalytic pocket. A structurally undefined N-terminal domain, dispensable for enzyme activity, mediates protein-protein interactions. Previously, reversible disulfide bonds were designed to assess whether locking the Top1 clamp around duplex DNA would restrict DNA strand rotation within the covalent Top1-DNA intermediate. The active site proxim","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Oct","modification":"2026-05-01T22:42:44.906Z","creation":"2019-03-27T00:18:44Z"},"accession":"S-EPMC2562070","cross_references":{"pubmed":["18693244"],"doi":["10.1074/jbc.M804826200","10.1074/jbc.m804826200"]}}