DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of DNA-templated DNA replication / Switching of origins to a post-replicative state / regulation of nuclear cell cycle DNA replication / negative regulation of DNA-templated DNA replication / DNA replication checkpoint signaling / attachment of mitotic spindle microtubules to kinetochore / Activation of the pre-replicative complex / positive regulation of chromatin binding ...DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of DNA-templated DNA replication / Switching of origins to a post-replicative state / regulation of nuclear cell cycle DNA replication / negative regulation of DNA-templated DNA replication / DNA replication checkpoint signaling / attachment of mitotic spindle microtubules to kinetochore / Activation of the pre-replicative complex / positive regulation of chromatin binding / regulation of DNA-templated DNA replication initiation / positive regulation of DNA replication / G1/S-Specific Transcription / negative regulation of DNA replication / regulation of DNA replication / regulation of mitotic cell cycle / negative regulation of cell cycle / DNA polymerase binding / transcription repressor complex / Assembly of the pre-replicative complex / animal organ morphogenesis / Orc1 removal from chromatin / kinetochore / histone deacetylase binding / transcription corepressor activity / mitotic cell cycle / DNA-binding transcription factor binding / nuclear body / cell division / negative regulation of DNA-templated transcription / chromatin binding / DNA binding / nucleoplasm / nucleus / cytoplasm / cytosol Similarity search - Function
Geminin coiled-coil domain / CDT1 Geminin-binding domain-like / Geminin/Multicilin / DNA replication factor Cdt1 / Geminin / DNA replication factor CDT1 like / DNA replication factor CDT1 like / DNA replication factor Cdt1, C-terminal / DNA replication factor Cdt1, C-terminal WH domain superfamily / DNA replication factor Cdt1 C-terminal domain ...Geminin coiled-coil domain / CDT1 Geminin-binding domain-like / Geminin/Multicilin / DNA replication factor Cdt1 / Geminin / DNA replication factor CDT1 like / DNA replication factor CDT1 like / DNA replication factor Cdt1, C-terminal / DNA replication factor Cdt1, C-terminal WH domain superfamily / DNA replication factor Cdt1 C-terminal domain / Single alpha-helices involved in coiled-coils or other helix-helix interfaces / Winged helix DNA-binding domain superfamily / Up-down Bundle / Mainly Alpha Similarity search - Domain/homology
Journal: Proc Natl Acad Sci U S A / Year: 2009 Title: Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing. Authors: V De Marco / P J Gillespie / A Li / N Karantzelis / E Christodoulou / R Klompmaker / S van Gerwen / A Fish / M V Petoukhov / M S Iliou / Z Lygerou / R H Medema / J J Blow / D I Svergun / S ...Authors: V De Marco / P J Gillespie / A Li / N Karantzelis / E Christodoulou / R Klompmaker / S van Gerwen / A Fish / M V Petoukhov / M S Iliou / Z Lygerou / R H Medema / J J Blow / D I Svergun / S Taraviras / A Perrakis / Abstract: All organisms need to ensure that no DNA segments are rereplicated in a single cell cycle. Eukaryotes achieve this through a process called origin licensing, which involves tight spatiotemporal ...All organisms need to ensure that no DNA segments are rereplicated in a single cell cycle. Eukaryotes achieve this through a process called origin licensing, which involves tight spatiotemporal control of the assembly of prereplicative complexes (pre-RCs) onto chromatin. Cdt1 is a key component and crucial regulator of pre-RC assembly. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication. Here, we address the mechanism of DNA licensing inhibition by Geminin, by combining X-ray crystallography, small-angle X-ray scattering, and functional studies in Xenopus and mammalian cells. Our findings show that the Cdt1:Geminin complex can exist in two distinct forms, a "permissive" heterotrimer and an "inhibitory" heterohexamer. Specific Cdt1 residues, buried in the heterohexamer, are important for licensing. We postulate that the transition between the heterotrimer and the heterohexamer represents a molecular switch between licensing-competent and licensing-defective states.
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