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SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation

Winterhalter, Charles; Stevens, Daniel; Fenyk, Stepan; Pelliciari, Simone; Marchand, Elie; Soultanas, Panos; Ilangovan, Aravindan; Murray, Heath

SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation Thumbnail


Authors

Charles Winterhalter

Daniel Stevens

Stepan Fenyk

Simone Pelliciari

Elie Marchand

PANOS SOULTANAS PANOS.SOULTANAS@NOTTINGHAM.AC.UK
Professor of Biological Chemistry

Aravindan Ilangovan

Heath Murray



Abstract

Bidirectional DNA replication from a chromosome origin requires the asymmetric loading of two helicases, one for each replisome. Our understanding of the molecular mechanisms underpinning helicase loading at bacterial chromosome origins is incomplete. Here we report both positive and negative mechanisms for directing helicase recruitment in the model organism Bacillus subtilis. Systematic characterization of the essential initiation protein DnaD revealed distinct protein interfaces required for homo-oligomerization, interaction with the master initiator protein DnaA, and interaction with the helicase co-loader protein DnaB. Informed by these properties of DnaD, we went on to find that the developmentally expressed repressor of DNA replication initiation, SirA, blocks the interaction between DnaD and DnaA, thereby restricting helicase recruitment from the origin during sporulation to inhibit further initiation events. These results advance our understanding of the mechanisms underpinning DNA replication initiation in B. subtilis, as well as guiding the search for essential cellular activities to target for antimicrobial drug design.

Citation

Winterhalter, C., Stevens, D., Fenyk, S., Pelliciari, S., Marchand, E., Soultanas, P., …Murray, H. (2023). SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation. Nucleic Acids Research, 51(9), 4302-4321. https://doi.org/10.1093/nar/gkac1060

Journal Article Type Article
Acceptance Date Oct 22, 2022
Online Publication Date Nov 23, 2022
Publication Date May 22, 2023
Deposit Date Oct 27, 2022
Publicly Available Date Mar 28, 2024
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Peer Reviewed Peer Reviewed
Volume 51
Issue 9
Pages 4302-4321
DOI https://doi.org/10.1093/nar/gkac1060
Keywords Chromosome, DnaD, DnaA, SirA, helicase, origin, replication
Public URL https://nottingham-repository.worktribe.com/output/12898606
Publisher URL https://academic.oup.com/nar/article/51/9/4302/6842904?login=false