Replication initiation proteins

The origins of all replicons contain a region whose sequence is rich in adenine and thymine residues (AT-rich). This site, also named DUE (DNA Unwinding Element), is the place where the initial destabilization (opening) of the double-stranded DNA (dsDNA) occurs and the replication complex is assembled. The opening of the duplex in the DUE creates single-stranded DNA (ssDNA), which is critical for replication initiation.

The AT-rich region, is bound by a number of proteins, either as ssDNA or dsDNA. Some proteins modify the origin’s architecture by binding to dsDNA (e.g. IHF, Fis); others bind to ssDNA and play crucial roles during DNA replication (e.g. DnaB, DnaG, PolIII holoenzyme) or by binding to dsDNA in the regulation of this process (e.g. SeqA, IciA, ArcA, HobH). Nevertheless, the main role of this region is to provide a structural scaffold for the assembly of the replication complex. The formation of the ssDNA scaffold for replication proteins is mediated by origin binding proteins (OBPs), which recognize and bind specific sequences within the replicon’s origin, close to the DUE element. Recent results have shown that the bacterial OBP, DnaA protein, apart from binding specific dsDNA sequences in the origin (the DnaA-boxes), also binds ssDNA DUE. This sequence-specific interaction with the ssDNA is essential for the opening of the origin and replication activity.

Want to learn more?

Wegrzyn et al. Nucleic Acids Research  42 (12), 7807–7818 (2014). Sequence-specific interactions of Rep proteins with ssDNA in the AT-rich region of the plasmid replication origin. LINK


Univ. Gdask: I. Konieczny´s Group