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The bacterial replication origin BUS promotes nucleobase capture

Lookup NU author(s): Dr Simone PelliciariORCiD, Dr Stepan Fenyk, Dr Daniel Stevens, Dr Charles WinterhalterORCiD, Dr Frederic SchrammORCiD, Sara Pintar, George Merces, Dr Tom Richardson, Dr Julia Hubbard, Professor Heath Murray

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2023, The Author(s).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).


Publication metadata

Author(s): Pelliciari S, Bodet-Lefevre S, Fenyk S, Stevens D, Winterhalter C, Schramm FD, Pintar S, Burnham DR, Merces G, Richardson TT, Tashiro Y, Hubbard J, Yardimci H, Ilangovan A, Murray H

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2023

Volume: 14

Issue: 1

Online publication date: 14/12/2023

Acceptance date: 21/11/2023

Date deposited: 18/01/2024

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-023-43823-w

DOI: 10.1038/s41467-023-43823-w

PubMed id: 38097584


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Funding

Funder referenceFunder name
BBSRC
Cancer Research UK FC001221
he Deutsche For- schungsgemeinschaft (SCHR 1684/1-1)
MRC
The Wellcome Trust
the Wellcome Trust (FC001221)
UK Medical Research Council FC001221
UKRI Altert16 BB/R000514/1

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