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Building A Replication Fork: Structural Synergy And Molecular Crosstalk Between Bacterial Initiators And Helicase Loaders
Author(s) -
Berger James M,
Mott Melissa,
Duderstadt Karl,
Erzberger Jan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.196.1
Subject(s) - dnab helicase , dnaa , helicase , replisome , microbiology and biotechnology , minichromosome maintenance , pre replication complex , dna replication , origin recognition complex , chemistry , primase , dna , origin of replication , biology , biophysics , eukaryotic dna replication , biochemistry , rna , gene , reverse transcriptase
The proper initiation of DNA replication is critical to all cells. Dedicated initiation factors belonging to the AAA+ ATPase superfamily are essential regulators of this process. In bacteria, ATP binding activates the DnaA initiator to trigger DNA melting and facilitate replisome assembly. Using structural approaches, we show that ATP induces conformational changes in DnaA that lead to the formation of a right‐handed, helical initiator assembly. This quaternary arrangement wraps origin DNA into a positive supercoil, and frees catalytic ATPase motifs for interacting with other proteins at filament ends. Parallel work on DnaC, the loading factor for the DnaB helicase, shows that this protein is close structural homolog of DnaA that also assembles into a helical structure, and that engages the initiator in an ATP‐dependent manner. Our findings provide a molecular framework for understanding how prokaryotic initiators transition between inactive monomer and functional multimer states, and implicate DnaC as an adaptor that helps ensure the proper spatial deposition of replicative hexameric helicases onto a replication origin.