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Article: Structural insight into the assembly and conformational activation of human origin recognition complex

TitleStructural insight into the assembly and conformational activation of human origin recognition complex
Authors
Issue Date2020
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/celldisc/
Citation
Cell Discovery, 2020, v. 6, article no. 88 How to Cite?
AbstractThe function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is reconfigured into a state competent for origin association remain largely unknown. Here, we present structural characterizations of human ORC1–5 and ORC2–5 assemblies. ORC2–5 exhibits a tightly autoinhibited conformation with the winged-helix domain of ORC2 completely blocking the central DNA-binding channel. The binding of ORC1 partially relieves the autoinhibitory effect of ORC2–5 through remodeling ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1 is highly flexible to sample a variety of conformations from inactive to potentially active states. These results provide insights into the detailed mechanisms regulating the autoinhibition of human ORC and its subsequent activation for DNA binding.
Persistent Identifierhttp://hdl.handle.net/10722/305120
ISSN
2023 Impact Factor: 13.0
2023 SCImago Journal Rankings: 4.198
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheng, J-
dc.contributor.authorLi, N-
dc.contributor.authorWang, X-
dc.contributor.authorHu, J-
dc.contributor.authorZhai, Y-
dc.contributor.authorGao, N-
dc.date.accessioned2021-10-05T02:40:00Z-
dc.date.available2021-10-05T02:40:00Z-
dc.date.issued2020-
dc.identifier.citationCell Discovery, 2020, v. 6, article no. 88-
dc.identifier.issn2056-5968-
dc.identifier.urihttp://hdl.handle.net/10722/305120-
dc.description.abstractThe function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is reconfigured into a state competent for origin association remain largely unknown. Here, we present structural characterizations of human ORC1–5 and ORC2–5 assemblies. ORC2–5 exhibits a tightly autoinhibited conformation with the winged-helix domain of ORC2 completely blocking the central DNA-binding channel. The binding of ORC1 partially relieves the autoinhibitory effect of ORC2–5 through remodeling ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1 is highly flexible to sample a variety of conformations from inactive to potentially active states. These results provide insights into the detailed mechanisms regulating the autoinhibition of human ORC and its subsequent activation for DNA binding.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/celldisc/-
dc.relation.ispartofCell Discovery-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleStructural insight into the assembly and conformational activation of human origin recognition complex-
dc.typeArticle-
dc.identifier.emailZhai, Y: zhai@hku.hk-
dc.identifier.authorityZhai, Y=rp02398-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41421-020-00232-3-
dc.identifier.pmid33298899-
dc.identifier.pmcidPMC7684300-
dc.identifier.scopuseid_2-s2.0-85096455486-
dc.identifier.hkuros325834-
dc.identifier.volume6-
dc.identifier.spagearticle no. 88-
dc.identifier.epagearticle no. 88-
dc.identifier.isiWOS:000595712400002-
dc.publisher.placeUnited Kingdom-

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