Bacterial chromosomes and their replication

Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli

“…Replication of the E. coli chromosome is initiated from oriC, from which the two nascent replication forks proceed bidirectionally, reaching completion at the terminus, ter region, after which two fully replicated chromosomes are segregated to daughter cells (for reviews, see Wolanski et al, 2014;Frimodt-Møller et al, 2024). The highly conserved DnaA protein initiates DNA replication by binding to specific "DnaA-boxes" in oriC, thereby facilitating strand opening at an AT-rich "DNA unwinding element, DUE" region (Bramhill and Kornberg, 1988), where two replisomes are subsequently assembled (Frimodt-Møller et al, 2024).…”

“…Replication of the E. coli chromosome is initiated from oriC, from which the two nascent replication forks proceed bidirectionally, reaching completion at the terminus, ter region, after which two fully replicated chromosomes are segregated to daughter cells (for reviews, see Wolanski et al, 2014;Frimodt-Møller et al, 2024). The highly conserved DnaA protein initiates DNA replication by binding to specific "DnaA-boxes" in oriC, thereby facilitating strand opening at an AT-rich "DNA unwinding element, DUE" region (Bramhill and Kornberg, 1988), where two replisomes are subsequently assembled (Frimodt-Møller et al, 2024). The E. coli DnaA protein contains four domains: an Nterminal protein interaction domain (Domain I); a linker domain (Domain II); an AAA+ ATPase domain, responsible for ATP/ADP binding and ATP hydrolysis (Domain III); and a double-stranded DNA binding domain (Domain IV) (Hansen and Atlung, 2018;Frimodt-Møller et al, 2024).…”

“…The highly conserved DnaA protein initiates DNA replication by binding to specific "DnaA-boxes" in oriC, thereby facilitating strand opening at an AT-rich "DNA unwinding element, DUE" region (Bramhill and Kornberg, 1988), where two replisomes are subsequently assembled (Frimodt-Møller et al, 2024). The E. coli DnaA protein contains four domains: an Nterminal protein interaction domain (Domain I); a linker domain (Domain II); an AAA+ ATPase domain, responsible for ATP/ADP binding and ATP hydrolysis (Domain III); and a double-stranded DNA binding domain (Domain IV) (Hansen and Atlung, 2018;Frimodt-Møller et al, 2024).…”

“…DnaA subsequently recruits two hexameric DnaB helicase complexes to the DUE region, which eventually leads to the assembly of two replisomes (Sakiyama et al, 2022). (For a thorough review of oriC structure and interactions with DnaA and other initiation factors, see Frimodt-Møller et al, 2024). It is essential that the initiation of chromosome replication is tightly controlled in the cell cycle, as the inability to initiate chromosome replication leads to chromosome loss (Botello and Nordstrom, 1998), whereas uncontrolled initiations are detrimental to genome integrity and result in chromosome breaks and cell death (Simmons et al, 2004;Charbon et al, 2014).…”

“…It is therefore not surprising that the initiation frequency is controlled by a stringent system of mechanisms to ensure that initiation occurs only once per cell cycle, and simultaneously from all cellular origins (Skarstad et al, 1986). For thorough reviews on mechanisms controlling the initiation of DNA replication in E. coli, see Katayama et al (2017), Atlung (2018), andFrimodt-Møller et al (2024).…”