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SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2023 May 22; Vol. 51 (9), pp. 4302-4321. - Publication Year :
- 2023
-
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.<br /> (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- DNA Replication
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
DnaB Helicases genetics
DnaB Helicases metabolism
Replication Origin
Bacillus subtilis genetics
Bacillus subtilis metabolism
Bacillus subtilis physiology
Bacterial Proteins genetics
Bacterial Proteins metabolism
DNA Helicases genetics
DNA Helicases metabolism
Spores, Bacterial metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 51
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 36416272
- Full Text :
- https://doi.org/10.1093/nar/gkac1060