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Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control.

J Liu·C L Smith·D DeRyckere·K DeAngelis·G S Martin·J M Berger
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Abstract

Cdc6/Cdc18 is a conserved and essential component of prereplication complexes. The 2.0 A crystal structure of an archaeal Cdc6 ortholog, in conjunction with a mutational analysis of the homologous Cdc18 protein from Schizosaccharomyces pombe, reveals novel aspects of Cdc6/Cdc18 function. Two domains of Cdc6 form an AAA+-type nucleotide binding fold that is observed bound to Mg.ADP. A third domain adopts a winged-helix fold similar to known DNA binding modules. Sequence comparisons show that the winged-helix domain is conserved in Orc1, and mutagenesis data demonstrate that this region of Cdc6/Cdc18 is required for function in vivo. Additional mutational analyses suggest that nucleotide binding and/or hydrolysis by Cdc6/Cdc18 is required not only for progression through S phase, but also for maintenance of checkpoint control during S phase.

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AllelesCell Cycle ProteinsCloning, MolecularCrystallographyDNA Mutational AnalysisDNA-Binding ProteinsFungal ProteinsGene Expression Regulation, FungalHistonesMolecular Sequence DataMutationNucleotidesOrigin Recognition ComplexPhenotypeProtein Structure, SecondaryProtein Structure, TertiaryReplication OriginS PhaseSaccharomyces cerevisiae ProteinsSchizosaccharomycesSchizosaccharomyces pombe ProteinsSequence Homology, Amino AcidStructure-Activity RelationshipJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J Liu, C L Smith, D DeRyckere, K DeAngelis, G S Martin, J M Berger. 2000. Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control.. https://doi.org/10.1016/s1097-2765(00)00062-9

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