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DNA stretching by bacterial initiators promotes replication origin opening

Author

Listed:
  • Karl E. Duderstadt

    (Biophysics Graduate Group, University of California, Berkeley, Berkeley, California 94720, USA)

  • Kevin Chuang

    (California Institute for Quantitative Biology, University of California, Berkeley, Berkeley, California 94720, USA)

  • James M. Berger

    (Biophysics Graduate Group, University of California, Berkeley, Berkeley, California 94720, USA
    California Institute for Quantitative Biology, University of California, Berkeley, Berkeley, California 94720, USA)

Abstract

Many replication initiators form higher-order oligomers that process host replication origins to promote replisome formation. In addition to dedicated duplex-DNA-binding domains, cellular initiators possess AAA+ (ATPases associated with various cellular activities) elements that drive functions ranging from protein assembly to origin recognition. In bacteria, the AAA+ domain of the initiator DnaA has been proposed to assist in single-stranded DNA formation during origin melting. Here we show crystallographically and in solution that the ATP-dependent assembly of Aquifex aeolicus DnaA into a spiral oligomer creates a continuous surface that allows successive AAA+ domains to bind and extend single-stranded DNA segments. The mechanism of binding is unexpectedly similar to that of RecA, a homologous recombination factor, but it differs in that DnaA promotes a nucleic acid conformation that prevents pairing of a complementary strand. These findings, combined with strand-displacement assays, indicate that DnaA opens replication origins by a direct ATP-dependent stretching mechanism. Comparative studies reveal notable commonalities between the approach used by DnaA to engage DNA substrates and other, nucleic-acid-dependent, AAA+ systems.

Suggested Citation

  • Karl E. Duderstadt & Kevin Chuang & James M. Berger, 2011. "DNA stretching by bacterial initiators promotes replication origin opening," Nature, Nature, vol. 478(7368), pages 209-213, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7368:d:10.1038_nature10455
    DOI: 10.1038/nature10455
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    Cited by:

    1. Simone Pelliciari & Salomé Bodet-Lefèvre & Stepan Fenyk & Daniel Stevens & Charles Winterhalter & Frederic D. Schramm & Sara Pintar & Daniel R. Burnham & George Merces & Tomas T. Richardson & Yumiko T, 2023. "The bacterial replication origin BUS promotes nucleobase capture," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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