SeqA

SeqA is a bacterial DNA replication control protein, primarily studied in Escherichia coli and related gamma-proteobacteria. It binds hemimethylated DNA, which is produced immediately after DNA replication when the parental strand is methylated by Dam methylase and the newly synthesized strand is not. SeqA preferentially binds to GATC sequences and does so cooperatively as a multimer, forming higher-order complexes that concentrate in the vicinity of the origin of replication, oriC.

Functionally, SeqA sequesters oriC and nearby DNA after replication to prevent premature reinitiation, thereby enforcing a refractory window before a new round of initiation can occur. The sequestration depends on the hemimethylated state; once Dam methylates the newly synthesized strand to give fully methylated DNA, SeqA releases and cells can initiate replication again in the next cell cycle. In this way SeqA couples DNA replication timing to the methylation state and the cell cycle.

Mechanistically, SeqA has an N-terminal region that mediates oligomerization and a C-terminal DNA-binding domain that recognizes hemimethylated GATC motifs. It can form SeqA foci at replication forks and oriC and functionally interacts with the initiator DnaA to regulate initiation timing. Binding is most pronounced shortly after replication and decreases as methylation proceeds.

Genetic and cellular effects include that deletion or inactivation of seqA leads to loss of origin sequestration, increased rates of reinitiation, abnormal chromosome copy number, and perturbations of cell cycle progression. SeqA is not essential for viability but contributes to replication fidelity and genome stability.

SeqA has been well characterized in E. coli and has homologs in related bacteria, where it plays a similar role in initiation control and DNA methylation coupling.