Structure and Function of Cdc6/Cdc18: Implications for Origin Recognition and Checkpoint Control

Mol Cell. 2000 Sep;6(3):637-48. doi: 10.1016/s1097-2765(00)00062-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Cell Cycle Proteins* / chemistry
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cloning, Molecular
  • Crystallography
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism
  • Molecular Sequence Data
  • Mutation / physiology
  • Nucleotides / metabolism
  • Origin Recognition Complex
  • Phenotype
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Replication Origin / physiology*
  • S Phase / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship

Substances

  • CDC6 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Histones
  • Nucleotides
  • Origin Recognition Complex
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • cdc18 protein, S pombe

Associated data

  • PDB/1FNN