title: The DnaC helicase loader is a dual ATP/ADP switch protein.
abstract: Helicases are transferred to replication origins by helicase loading factors. The Escherichia coli DnaC and eukaryotic Cdc6/18 helicase loaders contain ATP sites and are both members of the AAA+ family. One might expect that ATP is required for helicase loading; however, this study on DnaC illustrates that ATP is not actually needed for DnaC to load helicase onto single-strand DNA (ssDNA). In fact, it seems to be a paradox that after transfer of helicase to DNA, DnaC-ATP inhibits helicase action. In addition, ATP is required for DnaC function at an early step in oriC replication in which ATP stimulates ssDNA binding by DnaC, leading to expansion of the ssDNA bubble at the origin. Two cofactors, ssDNA and DnaB, trigger hydrolysis of ATP, converting DnaC to the ADP form that no longer inhibits DnaB. These observations have led to the idea that DnaC is a 'dual' switch protein, where both the ATP and the ADP forms are sequentially required for replication. This dual switching process may underlie the sensitivity of DnaB to even small fluctuations in DnaC levels.
authors.affiliation: Howard Hughes Medical Institute and Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Davey
authors.forename: Linhua
authors.initials: L
authors.lastname: Fang
authors.forename: Peter
authors.initials: P
authors.lastname: McInerney
authors.forename: Roxana E
authors.initials: RE
authors.lastname: Georgescu
authors.forename: Mike
authors.initials: M
authors.lastname: O'Donnell
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001435:Bacteriophages / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D053488:DnaB Helicases; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D018741:Replication Origin; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C071702:DnaC protein, E coli; D029968:Escherichia coli Proteins; D009687:Nuclear Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004265:DNA Helicases; D053488:DnaB Helicases