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- SASDAW3: Geminin:Cdt1 4:2 heterohexamer (Geminin + DNA replication factor ... -

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Basic information

Entry
Database: SASBDB / ID: SASDAW3
SampleGeminin:Cdt1 4:2 heterohexamer
  • Geminin (protein), Homo sapiens
  • DNA replication factor Cdt1 (protein), Cdt1, Homo sapiens
Function / homology
Function and homology information


DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of DNA-templated DNA replication / regulation of DNA replication origin binding / 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 / positive regulation of chromatin binding ...DNA replication preinitiation complex assembly / response to sorbitol / positive regulation of DNA-templated DNA replication / regulation of DNA replication origin binding / 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 / positive regulation of chromatin binding / regulation of DNA-templated DNA replication initiation / G1/S-Specific Transcription / negative regulation of DNA replication / regulation of DNA replication / negative regulation of cell cycle / Activation of the pre-replicative complex / DNA polymerase binding / regulation of mitotic cell cycle / transcription repressor complex / positive regulation of DNA replication / Assembly of the pre-replicative complex / animal organ morphogenesis / kinetochore / histone deacetylase binding / Orc1 removal from chromatin / 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 / cytosol / cytoplasm
Similarity search - Function
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 / Winged helix DNA-binding domain superfamily
Similarity search - Domain/homology
Geminin / DNA replication factor Cdt1
Similarity search - Component
Biological speciesHomo sapiens (human)
CitationJournal: 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.
Contact author
  • Maxim Petoukhov (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Models

Model #41
Type: atomic / Software: Crysol / Chi-square value: 8.637721
Search similar-shape structures of this assembly by Omokage search (details)

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Sample

SampleName: Geminin:Cdt1 4:2 heterohexamer / Sample MW: 107.53 kDa / Entity id: 38 / 39
BufferName: Tris75 / Concentration: 25.00 mM / pH: 7.5 / Composition: NaCl 200.000 mM
Entity #38Type: protein / Description: Geminin / Formula weight: 23.57 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: O75496
Sequence: MNPSMKQKQE EIKENIKNSS VPRRTLKMIQ PSASGSLVGR ENELSAGLSK RKHRNDHLTS TTSSPGVIVP ESSENKNLGG VTQESFDLMI KENPSSQYWK EVAEKRRKAL YEALKENEKL HKEIEQKDNE IARLKKENKE LAEVAEHVQY MAELIERLNG EPLDNFESLD ...Sequence:
MNPSMKQKQE EIKENIKNSS VPRRTLKMIQ PSASGSLVGR ENELSAGLSK RKHRNDHLTS TTSSPGVIVP ESSENKNLGG VTQESFDLMI KENPSSQYWK EVAEKRRKAL YEALKENEKL HKEIEQKDNE IARLKKENKE LAEVAEHVQY MAELIERLNG EPLDNFESLD NQEFDSEEET VEDSLVEDSE IGTCAEGTVS SSTDAKPCI
Entity #39Name: Cdt1 / Type: protein / Description: DNA replication factor Cdt1 / Formula weight: 60.39 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q9H211
Sequence: MEQRRVTDFF ARRRPGPPRI APPKLACRTP SPARPALRAP ASATSGSRKR ARPPAAPGRD QARPPARRRL RLSVDEVSSP STPEAPDIPA CPSPGQKIKK STPAAGQPPH LTSAQDQDTI SELASCLQRA RELGARVRAL KASAQDAGES CTPEAEGRPE EPCGEKAPAY ...Sequence:
MEQRRVTDFF ARRRPGPPRI APPKLACRTP SPARPALRAP ASATSGSRKR ARPPAAPGRD QARPPARRRL RLSVDEVSSP STPEAPDIPA CPSPGQKIKK STPAAGQPPH LTSAQDQDTI SELASCLQRA RELGARVRAL KASAQDAGES CTPEAEGRPE EPCGEKAPAY QRFHALAQPG LPGLVLPYKY QVLAEMFRSM DTIVGMLHNR SETPTFAKVQ RGVQDMMRRR FEECNVGQIK TVYPASYRFR QERSVPTFKD GTRRSDYQLT IEPLLEQEAD GAAPQLTASR LLQRRQIFSQ KLVEHVKEHH KAFLASLSPA MVVPEDQLTR WHPRFNVDEV PDIEPAALPQ PPATEKLTTA QEVLARARNL ISPRMEKALS QLALRSAAPS SPGSPRPALP ATPPATPPAA SPSALKGVSQ DLLERIRAKE AQKQLAQMTR CPEQEQRLQR LERLPELARV LRSVFVSERK PALSMEVACA RMVGSCCTIM SPGEMEKHLL LLSELLPDWL SLHRIRTDTY VKLDKAADLA HITARLAHQT RAEEGL

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Experimental information

BeamInstrument name: DORIS III X33 / City: Hamburg / : Germany / Type of source: X-ray synchrotronSynchrotron
DetectorName: MAR 345 Image Plate
Scan
Title: Cdt1:Geminin heterohexamer / Measurement date: Oct 5, 2006 / Unit: 1/nm /
MinMax
Q0.2034 4.991
ResultI0 from Guinier: 211.49 / Rg from Guinier: 3.8 nm / D max: 14 / Type of curve: single_conc /
ExperimentalPorod
MW90 kDa-
Volume-120 nm3

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