Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control.
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.
Liu
J
J
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Smith
C L
CL
DeRyckere
D
D
DeAngelis
K
K
Martin
G S
GS
Berger
J M
JM
D000483:Alleles; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003461:Crystallography; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009711:Nucleotides / Q000378:metabolism; D051738:Origin Recognition Complex; D010641:Phenotype; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018741:Replication Origin / Q000502:physiology*; D016196:S Phase / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006657:Histones; D009711:Nucleotides; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C082462:cdc18 protein, S pombe