ArticleNucleic acids research2021
Negative feedback for DARS2-Fis complex by ATP-DnaA supports the cell cycle-coordinated regulation for chromosome replication.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- The iron-sulfur accelerator YgfZ modulates genome-wide IHF-binding dynamics to regulate replication initiation inFrontiers in microbiology · 2026Article
- The Escherichia coli replication initiator DnaA is titrated on the chromosome.Nature communications · 2025Article
- Negative DNA supercoiling enhances DARS2 binding of DNA-bending protein IHF in the activation of Fis-dependent ATP-DnaA production.Nucleic acids research · 2025Article
- Direct single-cell observation of a keyScience advances · 2024Article
- The replication enhancer crtS depends on transcription factor Lrp for modulating binding of initiator RctB to ori2 of Vibrio cholerae.Nucleic acids research · 2024Article
- Read-through transcription of tRNA underlies the cell cycle-dependent dissociation of IHF from the DnaA-inactivating sequenceFrontiers in microbiology · 2024Article
- Cell cycle-coordinated maintenance of theEcoSal Plus · 2023Review
- Open Questions about the Roles of DnaA, Related Proteins, and Hyperstructure Dynamics in the Cell Cycle.Life (Basel, Switzerland) · 2023Review
- IHF and Fis asInternational journal of molecular sciences · 2023Review
- Regulatory elements coordinating initiation of chromosome replication to theProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins.International journal of molecular sciences · 2023Review
- The dimerization interface of initiator RctB governs chaperone and enhancer dependence of Vibrio cholerae chromosome 2 replication.Nucleic acids research · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Escherichia coli, the replication initiator DnaA oscillates between an ATP- and an ADP-bound state in a cell cycle-dependent manner, supporting regulation for chromosome replication. ATP-DnaA cooperatively assembles on the replication origin using clusters of low-affinity DnaA-binding sites. After initiation, DnaA-bound ATP is hydrolyzed, producing initiation-inactive ADP-DnaA. For the next round of initiation, ADP-DnaA binds to the chromosomal locus DARS2, which promotes the release of ADP, yielding the apo-DnaA to regain the initiation activity through ATP binding. This DnaA reactivation by DARS2 depends on site-specific binding of IHF (integration host factor) and Fis proteins and IHF binding to DARS2 occurs specifically during pre-initiation. Here, we reveal that Fis binds to an essential region in DARS2 specifically during pre-initiation. Further analyses demonstrate that ATP-DnaA, but not ADP-DnaA, oligomerizes on a cluster of low-affinity DnaA-binding sites overlapping the Fis-binding region, which competitively inhibits Fis binding and hence the DARS2 activity. DiaA (DnaA initiator-associating protein) stimulating ATP-DnaA assembly enhances the dissociation of Fis. These observations lead to a negative feedback model where the activity of DARS2 is repressed around the time of initiation by the elevated ATP-DnaA level and is stimulated following initiation when the ATP-DnaA level is reduced.
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