The bacterial replication origin BUS promotes nucleobase capture

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 Tashiro, Julia Hubbard, Hasan Yardimci, Aravindan Ilangovan () and Heath Murray ()
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Simone Pelliciari: Newcastle University
Salomé Bodet-Lefèvre: Queen Mary University of London
Stepan Fenyk: Newcastle University
Daniel Stevens: Newcastle University
Charles Winterhalter: Newcastle University
Frederic D. Schramm: Newcastle University
Sara Pintar: Newcastle University
Daniel R. Burnham: The Francis Crick Institute
George Merces: Newcastle University
Tomas T. Richardson: Newcastle University
Yumiko Tashiro: Queen Mary University of London
Julia Hubbard: Newcastle University
Hasan Yardimci: The Francis Crick Institute
Aravindan Ilangovan: Queen Mary University of London
Heath Murray: Newcastle University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Genome duplication is essential for the proliferation of cellular life and this process is generally initiated by dedicated replication proteins at chromosome origins. In bacteria, DNA replication is initiated by the ubiquitous DnaA protein, which assembles into an oligomeric complex at the chromosome origin (oriC) that engages both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) to promote DNA duplex opening. However, the mechanism of DnaA specifically opening a replication origin was unknown. Here we show that Bacillus subtilis DnaAATP assembles into a continuous oligomer at the site of DNA melting, extending from a dsDNA anchor to engage a single DNA strand. Within this complex, two nucleobases of each ssDNA binding motif (DnaA-trio) are captured within a dinucleotide binding pocket created by adjacent DnaA proteins. These results provide a molecular basis for DnaA specifically engaging the conserved sequence elements within the bacterial chromosome origin basal unwinding system (BUS).

Date: 2023
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DOI: 10.1038/s41467-023-43823-w

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