title: Regulation of minichromosome maintenance helicase activity by Cdc6.
abstract: Genetic studies, together with amino acid and structural similarities to the clamp loaders of DNA polymerase sliding clamps, have suggested that the Cdc6 protein may function as a loader for the eukaryotic replicative helicase, the minichromosome maintenance (MCM) complex. Thus, Cdc6 may act as the functional homologue of the bacterial DnaC that utilizes ATP hydrolysis to assemble the DnaB helicase at the origin. This report shows that the helicase activity of an MCM homologue from the archaeon Methanothermobacter thermautotrophicus is inhibited in the presence of the Cdc6 homologues. This inhibitory activity is dependent, as for DnaC, on ATP binding to Cdc6. Moreover, an intact Cdc6 winged helix domain is required for efficient inhibition. Two-hybrid analyses indicated that MCM and Cdc6 interact and that the interaction is mediated by the winged helix domain. Analysis of Cdc6 and MCM homologues from several archaea exhibited differences in the inhibitory activity suggesting divergence in function in Cdc6 and MCM homologues among the archaea.
authors.affiliation: University of Maryland Biotechnology Institute, Center for Advanced Research in Biotechnology, Rockville, Maryland 20850, USA.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Grabowski
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kasiviswanathan
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bell
authors.forename: Zvi
authors.initials: Z
authors.lastname: Kelman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D019843:Archaeal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D019847:Chromosomes, Archaeal; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D051738:Origin Recognition Complex; D010802:Phylogeny
chemical_list: D019843:Archaeal Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051738:Origin Recognition Complex; D000255:Adenosine Triphosphate; D004265:DNA Helicases; C403162:MCM protein, Methanobacterium thermoautotrophicum